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The article discusses how leukocytes, called neutrophils, look for activated platelets to initiate inflammation. Topics include the role of P-selectin glycoprotein ligand-1 (PSGL-1) in neutrophil polarization, the formation of a lamellipodia-rich domain, or leading edge, and a CD62L-enriched uropod, or hind edge, in activated leukocytes, and PSGL-1's control of intravascular motility and distribution of the receptors macrophage-1 antigen (Mac-1) and CXC chemokine 2 (CXCR2).

ISG15 is an interferon (IFN)-α/β--inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. Here, we describe human patients with inherited ISG15 deficiency and mycobacterial, but not viral, diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses that we tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes--granulocyte, in particular--reduced, the production of IFN-γ by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-γ--inducing secreted molecule for optimal antimycobacterial immunity. [ABSTRACT FROM AUTHOR]