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Department of Medicine, Division of Dermatology, University of California, San Diego and Veteran's Affairs Medical Center San Diego, CA 92161
Mast cells (MC) express cathelicidin antimicrobial peptides that act as broad-spectrum antibiotics and influence the immune defense of multiple epithelial surfaces. We hypothesized that MC help protect against skin infection through the expression of cathelicidin. The susceptibility of MC-deficient mice (Kit Wsh–/–) to invasive group A streptococcus (GAS) was compared with control mice. Following s.c. injection of GAS, MC-deficient mice had 30% larger skin lesions, 80% more lesional bacteria, and 30% more spleens positive for bacteria. In contrast to results obtained when GAS was injected into skin, no significant differences were noted between MC-deficient mice and control mice after GAS was applied topically, indicating that MC activity is most important after barrier penetration. To determine whether these differences were due to MC expression of cathelicidin, MC-deficient mice were reconstituted with MC derived from either wild-type or cathelicidin-deficient (Camp–/–) mice and challenged with GAS. Forty-eight hours after bacterial injection, mice that did not receive MC had an average lesion size of 200 mm2, mice reconstituted with wild-type MC showed lesions comparable to control mice (25 mm2), while mice reconstituted with Camp–/– MC showed an average lesion size of 120 mm2. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) analysis of cathelicidin peptide purified from mast cells defined this as a unique 28-aa peptide. Combined, these results show that MC confer defense against Gram-positive bacterial infection in the skin, a function mediated in part by the expression of a unique cathelicidin peptide.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants R01AR052728 and R01 AI052453, a Veteran's Affairs Merit Award (to R.L.G.), a Skin Research Grant from the Johnson & Johnson Skin Research Center, and a Career Development Grant from Dermatology Foundation (to A.D.).
2 Address correspondence and reprint requests to Dr. Richard L Gallo, Department of Medicine, Division of Dermatology, University of California, 3350 La Jolla Village Drive, San Diego, CA 92161. E-mail address: Rgallo{at}ucsd.edu
3 Abbreviations used in this paper: MC, mast cell; AMP, antimicrobial peptide; GAS, group A Streptococcus; THB, Todd-Hewitt; LB, Luria-Bertani; SELDI-TOF-MS, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry; LTA, lipoteichoic acid; SELDI-TOF-MS, surface-enhanced laser desorption/ionization time-of-flight-mass spectrometry; WT, wild type; CRAMP, cathelin-related antimicrobial peptide.
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