Skin dendritic cells increase in number during early response to wounding

Among the cells that may participate to wound response and wound healing, coordinate with other cell types, dendritic cells have been little studied until now and the least so in humans. This issue has been addressed on samples of wounded and control skin taken at autopsy and analyzed by immunohistochemistry and morphometry. Langerhans cell number in the epidermis and the relative volume of MHC II+ cells in the dermis increased transiently upon wounding, with a significant peak in the first and the second half hour after wounding respectively. Dermal MHC II+ cells became part of a perivascular mononuclear cell infiltrate visible in the subpapillary dermis since between 30 and 60 after wounding and which contained also MC. Cells at the periphery of the infiltrates were also DC-SIGN+ and CD11c+, i.e. were well differentiated connective tissue dendritic cells. Mast cells underwent degranulation associated to an increase in number in the first hours after wounding. These modifications of dendritic cells and mast cells and the respective tissue course suggest that epidermal and dermal dendritic cells participate to the early response to wounding in humans, coordinately with mast cells and possibly stimulating the recruitment and activation of the cells involved in injury response at later time points

Cell interactions between mast cells and dendritic cells in human skin wounds

The response to wounding passes through different phases and mast cells (MC) respond to injury since early [1]. These cells can interact with dendritic cells (DC) and lymphocytes in vitro to control immune responses [2], but possible interactions between MC and DC in the early response to wounding in vivo have not yet been investigated. To address this issue, cryosections of skin wounded since 0-24 h taken at autopsy were stained with fluorescent avidin (MC) and UEA-1 (Ulex europaeus-1 lectin: endothelium), and immunolabeled for MHC-II (DC), CD1a (Langerhans cells, i.e. epidermal DC) and PDGF (endothelium). Fluorescence microscopy was followed by computerized image analysis. Intact neighbor skin was used as control. Langerhans cells number increased significantly with a peak 5 min after wounding. The intensity of MHC-II expression and the relative volume of MHC-II+ cells in the dermis increased significantly since 5 min after wounding and remained high for several hours. These cells became part of a perivascular mononuclear cell infiltrate visible in the subpapillary dermis since 60 min after wounding, which contained also MC strictly close to MHC-II positive cells. Upon wounding the number of capillaries labeled by UEA-1 and for PDGF increased markedly. The results suggest that: immature cells residing in the epidermis may come to express CD1a quickly; DC recruitment and redistribution in the dermis may occur quite fast upon injury; the latter cells participate to the response to wounding since the early steps, coordinately with MC and close to capillaries. Therefore DC, together with MC, may be candidate to regulate early injury response in human skin. [1] Bacci et al. J. Forensic. Sci. 2011 (in press) [2] Dudeck et al. Eur. J. Immunol. 2011; doi: 10.1002/eji.201040994

Dendritic cells infiltrate the cardiac muscle fibers during myocardial infarction

Myocardial infarction (MI) consists in myocardial cell death due to prolonged ischemia. Partial ischemia at the periphery at the necrotic area may lead to “hibernating” myocardium, which may eventually recover. Upon necrosis an inflammatory a process starts [1], leading to healing through formation of a fibrous scar. Dendritic cells (DC) are involved in the regulation of immune responses and in the organization of inflammatory cell infiltrates in vascular wall, even independent of immune reactions. Another cell type involved in acute reaction to tissue injury are mast cells. The behaviour of DC and mast cells in myocardial infarction is still to be studied. To address this issue myocardial samples were taken at autopsy from the left ventricle of subjects respectively affected by (1) coronarosclerosis, (2) acute MI, (3) previous MI, and (4) traumatic lesions assumed as controls. Cryosections were stained with haematoxilin heosin and by immunohistochemistry. Fiber alterations consisting in loss of acidophilia and disappearance of nuclei and intercalar disks were found only in acute MI, while a cell infiltrate was found both in acute and previous MI. Massive infiltration of DC was found only in acute MI, while mast cells were similar to controls. These preliminary results suggest that DC react early to myocardial injury and therefore may be candidate regulators of the inflammatory and scarring response in this tissue and markers of acute myocardial infarction