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Mechanism of human polymorphonuclear leukocyte adhesion to serum-treated corneocytes
1Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan.
Abstract:
The accumulation of polymorphonuclear leukocytes (PMN) beneath the stratum corneum is a characteristic histopathologic finding in various aseptic pustular dermatoses. To elucidate the pathomechanism involved in this phenomenon, we investigated whether PMN also attach to a sheet of corneocytes in vitro. A 1-cm2 corneocyte sheet was attached to a sterile glass slide with double adhesive tape used for skin graft surgery before incubating with human serum. The PMN suspension then was applied to the sheet. Attached cells were stained with May-Grunwald-Giemsa and counted with a computer image analyzer. We quantitatively assessed PMN adhesion to the serum-treated corneocyte sheets, which was mediated by activation of the alternative complement pathway. Addition of either anti-CD18 or anti-CD11b antibody to the assay system resulted in a marked reduction of PMN adhesion. We also demonstrated immunohistochemically that iC3b was formed on the serum-treated corneocytes. These findings suggest that PMN attach to serum-treated corneocytes through an interaction of CR3 expressed on PMN with iC3b-coated corneocytes. In addition, we found that this adhesion was enhanced by activation of PMN with phorbol myristate acetate. From these results, we speculate that complement activation by corneocytes occurs in the cutaneous lesions of aseptic pustular dermatoses and that PMN can be stimulated by the interaction with iC3b-opsonized corneocytes as well as by chemotaxins, leading to damage of the surrounding epidermal keratinocytes.
Insights
Polymorphonuclear leukocytes (PMN) adhere to corneocytes via complement activation, a key process in aseptic pustular dermatoses. This interaction, mediated by CR3 on PMN and iC3b on corneocytes, contributes to skin inflammation.
Area of Science:
- Dermatology
- Immunology
- Cell Biology
Background:
- Aseptic pustular dermatoses feature polymorphonuclear leukocyte (PMN) accumulation under the stratum corneum.
- The precise mechanism of PMN adhesion to corneocytes in these conditions remains unclear.
Purpose of the Study:
- To investigate the in vitro adhesion of PMN to corneocytes.
- To elucidate the molecular pathways involved in PMN-corneocyte interactions.
Main Methods:
- Corneocyte sheets were incubated with human serum and PMN suspension.
- PMN adhesion was quantified using a computer image analyzer.
- Immunohistochemistry and blocking antibodies (anti-CD18, anti-CD11b) were employed.
Main Results:
- PMN adhesion to serum-treated corneocytes was observed and mediated by the alternative complement pathway.
- Complement fragment iC3b was detected on serum-treated corneocytes.
- Adhesion was significantly reduced by anti-CD18 or anti-CD11b antibodies, indicating CR3 involvement.
- PMN activation enhanced adhesion.
Conclusions:
- PMN attach to serum-treated corneocytes through the interaction of PMN's CR3 receptor with iC3b opsonized corneocytes.
- Complement activation on corneocytes likely contributes to PMN recruitment and activation in aseptic pustular dermatoses.
- This interaction may lead to epidermal keratinocyte damage.