One mechanism behind this distribution could be a prolonged lifespan of extravasated neutrophils, which may influence the relative distribution between the different leucocyte subsets. In favour of this view, a prolonged neutrophil survival has been reported after exposure to G-CSF [19–21] and following activation and clustering of CD11b/CD18 . During aseptic conditions, complement AZD0530 order activation can be induced by phagocytic cells or by the coagulation cascade [23, 24]. The TCC is the end product of complement activation, and in the present article, the presence of TCC confirmed complement activation in the skin chamber. The present results
are in line with previous findings on C5a, which is the counter cleavage product to C5b that participates in initiating TCC formation [3, 14]. IL-8 is a major chemoattractant for neutrophils, indirectly shown by an abolished migration of neutrophils to a local inflammation following intravenous administration of IL-8 . In the present article, a significant correlation between the concentration of IL-8 and in vivo as well as in vitro transmigration was present, which contrasts a former publication using
the skin chamber . Discrepancies between the two studies might reflect a multifactor dependence on different factors to regulate migration. In the present study, this was indicated by additional correlations between migration and the concentration of IL-1β, IL-6, IL-7 Fenbendazole and TNFα. On the other hand, no correlation was noted between the number of extravasated neutrophils check details and other chemokines such as MCP-1, MIP-1α, MIP-1β, interferon-gamma-induced protein 10 (IP-10) and eotaxin, reflecting the in vivo specificity of different classes of chemoattractants. The correlation between
IL-8 and neutrophil extravasation could potentially be mediated through the regulation of CD11b affinity and avidity. We have previously shown that CD11b is up-regulated on the surface of extravasated cells as a result of degranulation and that this is concomitant with production of IL-8, although the two events do not correlate . However, as neutrophil firm adhesion to ICAM-1 and fibrinogen is mediated by an activated form of CD11b/CD18 , we assessed CD11b activation using the CBRM1/5 monoclonal antibody. The expression of CBRM1/5 was first assessed on in vivo extravasated neutrophils collected from the 14-h skin blister. CBRM1/5 was significantly induced on in vivo extravasated neutrophils compared with peripheral neutrophils, strengthening the importance of CD11b activation for neutrophil in vivo extravasation. The long-term kinetics of CBRM1/5 exposure is not fully known, and it is likely that continuous alterations of CD11b occur exceeding the time of ligand interaction, and it is also not clear whether CD11b have a present role in an aseptic inflammation, beyond the time point of extravasation.