IntroductionConnective tissue-activating peptide III (CTAP-III) constitutes one of several molecular variants of -thromboglobulin-antigen (TG-Ag), a group of chemokines that differ by their degree of N-terminal truncation. Along with platelet factor 4 (PF-4/CXCL4) CTAP-III represents one of the major chemokines stored as preformed proteins in the alpha-granules of blood platelets. Both molecules become released into the environment immediately upon platelet activation and may arise to rather high local concentrations, as indicated by normal serum levels (PF-4, 0.4-1.9 M; CTAP-III, 1.6-4.8 M). 1 As suggested by our previous work, CTAP-III and PF-4 appear to have complementary functions in the early recruitment and activation of neutrophil granulocytes (neutrophils) (recently reviewed by Brandt et al 1,2 ). In contrast to ELR-positive chemokines such as IL-8/CXCL8, the ELR-negative chemokine PF-4 lacks the ability to induce chemotaxis and degranulation of primary granules in neutrophils 3 but very efficiently stimulates their firm adhesion to endothelial cells as well as the selective exocytosis of secondary granule markers. 3,4 Notably, the receptor for PF-4 on neutrophils is not a G protein-coupled receptor but a cell surface-expressed chondroitin sulfate proteoglycan. 5,6 In contrast, CTAP-III represents an inactive precursor of the neutrophilactivating peptide 2 (NAP-2/CXCL7), a typical ELR-positive chemokine that potently stimulates chemotaxis as well as degranulation in neutrophils 7-9 through interaction with its G proteincoupled receptors CXCR-2 and CXCR-1. [10][11][12] To convert CTAP-III into its active derivative, limited truncation by enzymatic proteolysis is required. Intriguingly, neutrophils themselves are the major blood cells to cleave CTAP-III into NAP-2 by removing a stretch of 15 amino acids from the N terminus of the precursor. 9,13 So far all evidence suggests that cell surface-bound cathepsin G (CathG), a chymotryptic serine protease also found in primary neutrophil granules, is responsible for CTAP-III processing. 9,13-15 Among blood cells, only monocytes share the ability of neutrophils to convert CTAP-III into NAP-2, 13,16 albeit to a considerably lower extent than neutrophils, which argues against a relevant role for monocytes in NAP-2 formation during early inflammation. 13 In contrast to the well-characterized processing capacity of blood leukocytes, the contribution of cells from the surrounding vascular tissue has remained largely unclear. We have previously shown that at least endothelial cells are inactive in this respect. 17 For personal use only. on April 29, 2019. by guest www.bloodjournal.org From has also been reported that MC degranulation in allergenchallenged animals is accompanied by the simultaneous intravascular aggregation of platelets 21 and that both cell types are particularly involved in the concomitant delayed invasion of neutrophils. 22,23 Considering the observation that in response to allergen exposure platelet markers CTAP-III and PF-4 are secreted into the ...