Secondary necrosis of apoptotic neutrophils induced by the human cathelicidin LL-37 is not proinflammatory to phagocytosing macrophages

Journal of Leukocyte Biology

Volumn 86, Issue 4, 2009, Pages 891-902

  Li, Hsin Ni ^a   Barlow, Peter G ^a   Bylund, Johan ^b   Mackellar, Annie ^a   Björstad, Åse ^b   Conlon, James ^a   Hiemstra, Pieter S ^c   Haslett, Chris ^a   Gray, Mohini ^a   Simpson, A John ^a   Rossi, Adriano G ^a   Davidson, Donald J ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b UNIVERSITY OF GOTHENBURG   (Sweden)

^c LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Antimicrobial peptide; Cationic host defense peptide; Efferocytosis; Inflammation; Innate immunity

Indexed keywords

CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37;

APOPTOSIS; ARTICLE; GRANULE CELL; HOST; HOST RESISTANCE; HUMAN; HUMAN CELL; IMMUNOMODULATION; INFLAMMATION; MACROPHAGE; NECROSIS; PHAGOCYTOSIS; PRIORITY JOURNAL;

APOPTOSIS; CATHELICIDINS; CELL DEGRANULATION; HUMANS; MACROPHAGES; NECROSIS; NEUTROPHILS; PHAGOCYTOSIS;

EID: 70349635632     PISSN: 07415400     EISSN: None     Source Type: Journal    
DOI: 10.1189/jlb.0209050     Document Type: Article

References (53)

1. Haslett, C. (1999) Granulocyte apoptosis and its role in the resolution and control of lung inflammation. Am. J. Respir. Crit. Care Med. 160, S5-11.
2. Leitch, A. E., Duffin, R., Haslett, C., Rossi, A. G. (2008) Relevance of granulocyte apoptosis to resolution of inflammation at the respiratory mucosa. Mucosal Immunol. 1, 350-363.
3. Savill, J., Dransfield, I., Gregory, C., Haslett, C. (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat. Rev. Immunol. 2, 965-975. (Pubitemid 37323217)
4. Voll, R. E., Herrmann, M., Roth, E. A., Stach, C., Kalden, J. R., Girkontaite, I. (1997) Immunosuppressive effects of apoptotic cells. Nature 390, 350-351.
5. Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., Henson, P. M. (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-β, PGE2, and PAF. J. Clin. Invest. 101, 890-898. (Pubitemid 28096086)
6. Huynh, M. L., Fadok, V. A., Henson, P. M. (2002) Phosphatidylserine- dependent ingestion of apoptotic cells promotes TGF-β1 secretion and the resolution of inflammation. J. Clin. Invest. 109, 41-50.
7. Serhan, C. N., Savill, J. (2005) Resolution of inflammation: the beginning programs the end. Nat. Immunol. 6, 1191-1197.
8. Bianchi, S. M., Dockrell, D. H., Renshaw, S. A., Sabroe, I., Whyte, M. K. (2006) Granulocyte apoptosis in the pathogenesis and resolution of lung disease. Clin. Sci. (Lond.) 110, 293-304. (Pubitemid 43341631)
9. Rossi, A. G., Sawatzky, D. A., Walker, A., Ward, C., Sheldrake, T. A., Riley, N. A., Caldicott, A., Martinez-Losa, M., Walker, T. R., Duffin, R., Gray, M., Crescenzi, E., Martin, M. C., Brady, H. J., Savill, J. S., Dransfield, I., Haslett, C. (2006) Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat. Med. 12, 1056-1064. (Pubitemid 44353387)
10. Barlow, P. G., Li, Y., Wilkinson, T. S., Bowdish, D. M., Lau, Y. E., Cosseau, C., Haslett, C., Simpson, A. J., Hancock, R. E., Davidson, D. J. (2006) The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system. J. Leukoc. Biol. 80, 509-520. (Pubitemid 44835784)
11. Nagaoka, I., Tamura, H., Hirata, M. (2006) An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7. J. Immunol. 176, 3044-3052. (Pubitemid 43306966)
12. Sorensen, O., Arnljots, K., Cowland, J. B., Bainton, D. F., Borregaard, N. (1997) The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Blood 90, 2796-2803. (Pubitemid 27413490)
13. Sorensen, O. E., Follin, P., Johnsen, A. H., Calafat, J., Tjabringa, G. S., Hiemstra, P. S., Borregaard, N. (2001) Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 97, 3951-3959.
14. Bowdish, D. M., Davidson, D. J., Hancock, R. E. (2006) Immunomodulatory properties of defensins and cathelicidins. Curr. Top. Microbiol. Immunol. 306, 27-66.
15. Scott, M. G., Davidson, D. J., Gold, M. R., Bowdish, D., Hancock, R. E. (2002) The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J. Immunol. 169, 3883-3891.
16. Fukumoto, K., Nagaoka, I., Yamataka, A., Kobayashi, H., Yanai, T., Kato, Y., Miyano, T. (2005) Effect of antibacterial cathelicidin peptide CAP18/LL-37 on sepsis in neonatal rats. Pediatr. Surg. Int. 21, 20-24. (Pubitemid 40169453)
17. De Yang, Chen, Q., Schmidt, A. P., Anderson, G. M., Wang, J. M., Wooters, J., Oppenheim, J. J., Chertov, O. (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J. Exp. Med. 192, 1069-1074. (Pubitemid 30765699)
18. Kurosaka, K., Chen, Q., Yarovinsky, F., Oppenheim, J. J., Yang, D. (2005) Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant. J. Immunol. 174, 6257-6265. (Pubitemid 40663818)
19. Elssner, A., Duncan, M., Gavrilin, M., Wewers, M. D. (2004) A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1β processing and release. J. Immunol. 172, 4987-4994. (Pubitemid 38456425)
20. Mookherjee, N., Brown, K. L., Bowdish, D. M., Doria, S., Falsafi, R., Hokamp, K., Roche, F. M., Mu, R., Doho, G. H., Pistolic, J., Powers, J. P., Bryan, J., Brinkman, F. S., Hancock, R. E. (2006) Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J. Immunol. 176, 2455-2464. (Pubitemid 43201696)
21. Niyonsaba, F., Someya, A., Hirata, M., Ogawa, H., Nagaoka, I. (2001) Evaluation of the effects of peptide antibiotics human β-defensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells. Eur. J. Immunol. 31, 1066-1075.
22. Heilborn, J. D., Nilsson, M. F., Kratz, G., Weber, G., Sorensen, O., Borregaard, N., Stahle-Backdahl, M. (2003) The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J. Invest. Dermatol. 120, 379-389. (Pubitemid 36298423)
23. Koczulla, R., Von Degenfeld, G., Kupatt, C., Krotz, F., Zahler, S., Gloe, T., Issbrucker, K., Unterberger, P., Zaiou, M., Lebherz, C., Karl, A., Raake, P., Pfosser, A., Boekstegers, P., Welsch, U., Hiemstra, P. S., Vogelmeier, C., Gallo, R. L., Clauss, M., Bals, R. (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J. Clin. Invest. 111, 1665-1672. (Pubitemid 38057748)
24. Davidson, D. J., Currie, A. J., Reid, G. S., Bowdish, D. M., MacDonald, K. L., Ma, R. C., Hancock, R. E., Speert, D. P. (2004) The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J. Immunol. 172, 1146-1156.
25. An, L. L., Yang, Y. H., Ma, X. T., Lin, Y. M., Li, G., Song, Y. H., Wu, K. F. (2005) LL-37 enhances adaptive antitumor immune response in a murine model when genetically fused with M-CSFR(J6-1) DNA vaccine. Leuk. Res. 29, 535-543. (Pubitemid 40327242)
26. Lau, Y. E., Bowdish, D. M., Cosseau, C. C., Hancock, R. E., Davidson, D. J. (2006) Apoptosis of airway epithelial cells: human serum sensitive induction by the cathelicidin LL-37. Am. J. Respir. Cell Mol. Biol. 34, 399-409.
27. Aarbiou, J., Tjabringa, G. S., Verhoosel, R. M., Ninaber, D. K., White, S. R., Peltenburg, L. T., Rabe, K. F., Hiemstra, P. S. (2006) Mechanisms of cell death induced by the neutrophil antimicrobial peptides α-defensins and LL-37. Inflamm. Res. 55, 119-127.
28. Putsep, K., Carlsson, G., Boman, H. G., Andersson, M. (2002) Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet 360, 1144-1149. (Pubitemid 35246490)
29. Nizet, V., Ohtake, T., Lauth, X., Trowbridge, J., Rudisill, J., Dorschner, R. A., Pestonjamasp, V., Piraino, J., Huttner, K., Gallo, R. L. (2001) Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414, 454-457. (Pubitemid 34173727)
30. Iimura, M., Gallo, R. L., Hase, K., Miyamoto, Y., Eckmann, L., Kagnoff, M. F. (2005) Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J. Immunol. 174, 4901-4907. (Pubitemid 40504574)
31. Chromek, M., Slamova, Z., Bergman, P., Kovacs, L., Podracka, L., Ehren, I., Hokfelt, T., Gudmundsson, G. H., Gallo, R. L., Agerberth, B., Brauner, A. (2006) The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat. Med. 12, 636-641. (Pubitemid 43865231)
32. Schaller-Bals, S., Schulze, A., Bals, R. (2002) Increased levels of antimicrobial peptides in tracheal aspirates of newborn infants during infection. Am. J. Respir. Crit. Care Med. 165, 992-995. (Pubitemid 34774670)
33. Bals, R., Weiner, D. J., Moscioni, A. D., Meegalla, R. L., Wilson, J. M. (1999) Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide. Infect. Immun. 67, 6084-6089. (Pubitemid 29508140)
34. Chen, C. I., Schaller-Bals, S., Paul, K. P., Wahn, U., Bals, R. (2004) β-Defensins and LL-37 in bronchoalveolar lavage fluid of patients with cystic fibrosis. J. Cyst. Fibros. 3, 45-50. (Pubitemid 38397023)
35. Lande, R., Gregorio, J., Facchinetti, V., Chatterjee, B., Wang, Y. H., Homey, B., Cao, W., Wang, Y. H., Su, B., Nestle, F. O., Zal, T., Mellman, I., Schroder, J. M., Liu, Y. J., Gilliet, M. (2007) Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449, 564-569. (Pubitemid 47525141)
36. Anderson, R. L., Hiemstra, P. S., Ward, C., Forrest, I. A., Murphy, D., Proud, D., Lordan, J., Corris, P. A., Fisher, A. J. (2008) Antimicrobial peptides in lung transplant recipients with bronchiolitis obliterans syndrome. Eur. Respir. J. 32, 670-677.
37. Nell, M. J., Tjabringa, G. S., Wafelman, A. R., Verrijk, R., Hiemstra, P. S., Drijfhout, J. W., Grote, J. J. (2006) Development of novel LL-37 derived antimicrobial peptides with LPS and LTA neutralizing and antimicrobial activities for therapeutic application. Peptides 27, 649-660.
38. Zhang, Z., Cherryholmes, G., Shively, J. E. (2008) Neutrophil secondary necrosis is induced by LL-37 derived from cathelicidin. J. Leukoc. Biol. 84, 780-788.
39. Jersmann, H. P., Ross, K. A., Vivers, S., Brown, S. B., Haslett, C., Dransfield, I. (2003) Phagocytosis of apoptotic cells by human macrophages: analysis by multiparameter flow cytometry. Cytometry A 51, 7-15. (Pubitemid 37517306)
40. Liu, Y., Cousin, J. M., Hughes, J., Van Damme, J., Seckl, J. R., Haslett, C., Dransfield, I., Savill, J., Rossi, A. G. (1999) Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes. J. Immunol. 162, 3639-3646. (Pubitemid 29313619)
41. Bjorstad, A., Askarieh, G., Brown, K. L., Christenson, K., Forsman, H., Onnheim, K., Li, H. N., Teneberg, S., Maier, O., Hoekstra, D., Dahlgren, C., Davidson, D. J., Bylund, J. (2009) The host defence peptide LL-37 selectively permeabilizes apoptotic leukocytes. Antimicrob. Agents Chemother. 53, 1027-1038.
42. Klein, J. B., Rane, M. J., Scherzer, J. A., Coxon, P. Y., Kettritz, R., Mathiesen, J. M., Buridi, A., McLeish, K. R. (2000) Granulocyte-macrophage colony-stimulating factor delays neutrophil constitutive apoptosis through phosphoinositide 3-kinase and extracellular signal-regulated kinase pathways. J. Immunol. 164, 4286-4291. (Pubitemid 30215090)
43. Sabroe, I., Prince, L. R., Jones, E. C., Horsburgh, M. J., Foster, S. J., Vogel, S. N., Dower, S. K., Whyte, M. K. (2003) Selective roles for Toll-like receptor (TLR)2 and TLR4 in the regulation of neutrophil activation and life span. J. Immunol. 170, 5268-5275. (Pubitemid 36554761)
44. Fadok, V. A., Bratton, D. L., Guthrie, L., Henson, P. M. (2001) Differential effects of apoptotic versus lysed cells on macrophage production of cytokines: role of proteases. J. Immunol. 166, 6847-6854. (Pubitemid 32467230)
45. Cocco, R. E., Ucker, D. S. (2001) Distinct modes of macrophage recognition for apoptotic and necrotic cells are not specified exclusively by phosphatidylserine exposure. Mol. Biol. Cell 12, 919-930.
46. Krysko, D. V., D'Herde, K., Vandenabeele, P. (2006) Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis 11, 1709-1726. (Pubitemid 44371047)
47. Patel, V. A., Longacre, A., Hsiao, K., Fan, H., Meng, F., Mitchell, J. E., Rauch, J., Ucker, D. S., Levine, J. S. (2006) Apoptotic cells, at all stages of the death process, trigger characteristic signaling events that are divergent from and dominant over those triggered by necrotic cells: implications for the delayed clearance model of autoimmunity. J. Biol. Chem. 281, 4663-4670. (Pubitemid 43847725)
48. Kazama, H., Ricci, J. E., Herndon, J. M., Hoppe, G., Green, D. R., Ferguson, T. A. (2008) Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein. Immunity 29, 21-32. (Pubitemid 351952462)
49. Lucas, M., Stuart, L. M., Zhang, A., Hodivala-Dilke, K., Febbraio, M., Silverstein, R., Savill, J., Lacy-Hulbert, A. (2006) Requirements for apoptotic cell contact in regulation of macrophage responses. J. Immunol. 177, 4047-4054. (Pubitemid 44359938)
50. Borregaard, N., Cowland, J. B. (1997) Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 89, 3503-3521. (Pubitemid 27227073)
51. Ong, P. Y., Ohtake, T., Brandt, C., Strickland, I., Boguniewicz, M., Ganz, T., Gallo, R. L., Leung, D. Y. (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N. Engl. J. Med. 347, 1151-1160.
52. Li, X., Li, Y., Han, H., Miller, D. W., Wang, G. (2006) Solution structures of human LL-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region. J. Am. Chem. Soc. 128, 5776-5785. (Pubitemid 43724381)
53. Murakami, M., Lopez-Garcia, B., Braff, M., Dorschner, R. A., Gallo, R. L. (2004) Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J. Immunol. 172, 3070-3077. (Pubitemid 38263696)