N its activity within the calcium flux assay, but also that the truncated rHuMig is unable to block the activity on the full-length protein. This suggests that decreased receptor binding can be the basis for diminished activity shown by the truncated rHuMig. Interactions with cell-surface glycosaminoglycans including heparan sulfate may be important in the binding of HuMig to its receptor, and these interactions will be anticipated to be impacted by deletion of HuMig’s C O O H terminus. Since COOH-terminal cleavage impacts the activity of rHuMig, at least with respect to calcium flux in T cells, such processing could nicely possess a regulatory function in vivo. Although we have demonstrated that this processing is occurring just before secretion for the C H O cells in culture, this doesn’t do away with the possibility that the susceptibility of HuMig to an inactivating proteolytic cleavage is applied in vivo to limit the duration of HuMig’s activity just after its secretion. Inside the case of IL-8, one example is, it has been reported that inactivation can occur as the result ofprotease(s) present in serosal fluid (67). If, in vivo, proteolytic processing of HuMig happens only ahead of secretion, it raises the question as to what benefit would be conferred by secreting types of HuMig withvarying specific activities. Taking into consideration the likelihood that the truncated types o f H u M i g will bind less readily to glycosaminoglycans in extracellular matrix and on cell surfaces, as in comparison to the full-length HuMig, it is doable that in tissue, because the distance in the HuMig-producing cell increases, the immobilized types o f H u M i g will be those much more truncated and much less active. This would add another dimension to a chemotactic gradient that would n o w be formed not merely by modifications in ligand concentration, or density, but additionally by adjustments inside the certain activities o f the immobilized ligands, with specific activities escalating as the distance for the HuMig-producing cell diminishes. H u M i g is induced in macrophages (18) by the FCGR2A/CD32a Proteins Biological Activity lymphocyte solution I F N – and H u M i g in turn targets activated T cells. Experiments in vivo have demonstrated lymphocyte recruitment into skin at internet sites o f I F N – y injection (68), andour benefits make Mig a affordable candidate for mediating these effects. Similarly, our demonstration that rHuMig can function as a chemotactic element for TIL tends to make H u M i g a candidate for mediating the lymphocyte chemotaxis induced by supernatants from explanted tumors (69) and for mediating lymphocyte infiltration of tumors in vivo. Chemokines have been recommended to play crucial roles in regulating the adhesion as well as the migration o f leukocytes as component o f the multistep approach o f IFN-alpha 4 Proteins web leukocyte trafficking. In particular, chemokines are well-suited to provide a crucial component o f the specificity that is certainly needed for the differing patterns o f recruitment and recirculation noticed for subpopulations o f lymphocytes (ten). W e might be keen on figuring out what part Mig might have in the trafficking o f T lymphocyte subsets and what effects Mig might have on aspects o f T cell physiology usually.We are indebted to F. William Studier for supplying the pET vectors and bacterial strains; to Se-Jin Lee for the pMSXND vector, the parent CHO cells, and useful discussions; to William Lane as well as the Harvard Microbiochemistry Facility for NH2-terminal sequencing and mass spectrometry; to Robert Siliciano for F14.38 and also other T cell clones and for the B lymphoblastoid cell lines; to.