Keratinocytes store the antimicrobial peptide cathelicidin in lamellar bodies
Open accessAbstract
Innate immune defense against microbial pathogens occurs by physical barriers, by recruitment of cells such as neutrophils, NK cells, and macrophages, and by secretion of molecules with antimicrobial activity. Such molecules are produced by various epithelia including skin. The importance of antimicrobial peptides has been shown in cathelicidin-deficient mice, which have increased susceptibility to skin infection by Streptococcus. Although keratinocytes increase cathelicidin expression upon injury, their role relative to neutrophil cathelicidin and their sites of peptide storage and activation have not been elucidated. Herein, it is reported that cathelicidin predominantly resides in granules of the superficial epidermis and partially localizes in lamellar bodies as determined by immunogold electron microscopy and immunoblot of lamellar bodies isolated from mice. In cultured keratinocytes, cathelicidin displays a granular distribution and partially localizes within the Golgi apparatus. Cathelicidin processing can be observed by western blot analysis in keratinocyte extracts but not in conditioned media. Further, fluorescent bacteria colocalize with cathelicidin in granules both intracellularly and at the cell surface. These observations illustrate the immune defense potential of keratinocytes acting directly through storage and processing of antimicrobial peptides.
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Many antimicrobial peptides are stored in the lysosomes of macrophages and polymorphonuclear leukocytes, where they are part of the oxygen-independent activity against pathogens.
“Many antimicrobial peptides are stored in the lysosomes of macrophages and polymorphonuclear leukocytes, where they are part of the oxygen-independent activity against pathogens [177,178].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [177]
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Self-citationS100A15, an Antimicrobial Protein of the Skin: Regulation by E. coli through Toll-Like Receptor 4
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Self-citationLipid abnormalities and lipid-based repair strategies in atopic dermatitis
Elias, P. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.10.001 · Cited by 78 · see citing works
Epidermal BarriersPreprint
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Lamellar Bodies: The Key to Cutaneous Barrier Function
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Exploring the skin microbiome in atopic dermatitis pathogenesis and disease modification
Hülpüsch, C., Rohayem, R., Reiger, M., & Traidl‐Hoffmann, C. (2024) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2024.04.029 · Cited by 79 · see citing works
The Host Defense Peptide Cathelicidin Is Required for NK Cell-Mediated Suppression of Tumor Growth
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Role of the calcium-sensing receptor in calcium regulation of epidermal differentiation and function
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Therapeutic Implications of a Barrier-based Pathogenesis of Atopic Dermatitis
Elias, P. M. (2010) · Annals of Dermatology · doi:10.5021/ad.2010.22.3.245 · Cited by 66 · see citing works
Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis
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Borkowski, A. W., Park, K., Uchida, Y., & Gallo, R. L. (2013) · Journal of Investigative Dermatology · doi:10.1038/jid.2013.39 · Cited by 59 · see citing works
Self-citationThe role of altered cutaneous immune responses in the induction and persistence of rosacea
Margalit, A., Kowalczyk, M. J., Żaba, R. W., & Kavanagh, K. A. (2015) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2015.12.006 · Cited by 58 · see citing works
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The Coordinated Response of the Physical and Antimicrobial Peptide Barriers of the Skin
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Self-citationMin, S.-Y., Park, C.-H., Yu, H.-W., & Park, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168431 · Cited by 56 · see citing works
Molecular Genetic of Atopic Dermatitis : An Update
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Role of host-defence peptides in eye diseases
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Molecular basis of the skin barrier structures revealed by electron microscopy
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Excessive localized leukotriene B4 levels dictate poor skin host defense in diabetic mice
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Antimicrobial Peptides, Infections and the Skin Barrier
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Vitamin D, the Cutaneous Barrier, Antimicrobial Peptides and Allergies: Is There a Link?
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Antimicrobial anxiety: the impact of stress on antimicrobial immunity
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Preparation and application of graphene-based wearable sensors
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In vivo expression of antimicrobial peptides in atopic dermatitis
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Evidence that stress to the epidermal barrier influenced the development of pigmentation in humans
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The Epidermal Barrier in Atopic Dermatitis
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Control of cutaneous antimicrobial peptides by vitamin D3
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Innate Immunity: A Cutaneous Perspective
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Development of Human Lung Induction Models for Air Pollutants’ Toxicity Assessment
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Atopic Dermatitis: Pathophysiology
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- Authors
- Braff, M. H., Nardo, A. D., & Gallo, R. L.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Gallo, Richard L.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 124
- Issue
- 2
- Pages
- 394-400
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2066902095
- Cited by
- 213
- References
- 36
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 11 · 2023: 3 · 2022: 9 · 2021: 16 · 2020: 9 · 2019: 7 · 2018: 9 · 2017: 3 · 2016: 11 · 2015: 13 · 2014: 7 · 2013: 21 · 2012: 12
- FWCI
- 11.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI 052453)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-07202, T32DK007202)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 45676, R01AR045676)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Keywords
- cathelicidin, keratinocytes, lamellar bodies, antimicrobial peptides, innate immunity, skin barrier, Golgi apparatus, peptide processing
- MeSH terms
- Epidermal Cells, Cells, Cultured, Cytoplasmic Granules, Escherichia coli, Escherichia coli Infections, Golgi Apparatus, Humans, Microscopy, Electron, Microscopy, Fluorescence, Protein Precursors, Keratinocytes, Antimicrobial Cationic Peptides, Cathelicidins
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