No abstract

Neutrophils play important roles in host defense against all classes of infectious agents but, paradoxically, they are also involved in the pathology of various inflammatory conditions. Their microbicidal armory consists of oxidative and nonoxidative processes that are activated simultaneously upon phagocytosis. Although destruction of infectious agents occurs intracellularly, release of cytotoxic molecules into the extracellular milieu can damage body tissues. Neutrophils are heterogeneous. Subpopulations exist in various stages from dormant to primed to fully activated. The activities of neutrophils are regulated locally in microenvironments and systemically by a plethora of mediators including cytokines, "classical" neuroendocrine hormones, and bioactive lipids. The net response depends on a complex balance of stimulatory and inhibitory pathways that are regulated by these mediators. Although some effector and regulatory pathways are vital, considerable redundancy is also evident. Identification of the essential mediators and the unraveling of any interactions may be the keys to understanding the neutrophil paradox and developing therapeutic strategies that optimize microbial killing and minimize host tissue damage. Finally, reports that neutrophils can act as drug delivery vectors and that their function is influenced by stress and other lifestyle factors suggest that new homeostatic functions for these cells, outside their traditional roles in host defense and inflammation, remain to be identified: some are speculated on here.

Framework monoclonal antibodies have identified a population of human lymphocytes that express the T3 glycoprotein but not the T-cell receptor (TCR) alpha- and beta-subunits. Chemical crosslinking experiments reveal that these lymphocytes express novel T3-associated polypeptides, one of which appears to be the product of the T gamma gene. The other polypeptide may represent a fourth TCR subunit, designated T delta.

A 6.75-kilobase human hepatoma-derived basic fibroblast growth factor (bFGF) cDNA was cloned and sequenced. An amino-terminal sequence generated from a purified hepatoma bFGF was found to correspond to the nucleotide sequence and to begin 8 amino acids upstream from the putative methionine start codon thought to initiate a 154-amino acid bFGF translation product. This sequence suggests that a form of bFGF of at least 163 amino acids exists. The hepatoma cDNA was transcribed in vitro into RNA; in vitro translation of this RNA generated three forms of bFGF with molecular masses of 18, 21, and 22.5 kDa. By use of in vitro mutagenesis, it was found that the 22.5-kDa bFGF and possibly the 21-kDa form were initiated with CUG start codons. The 18-kDa bFGF was initiated with an AUG codon. By transfecting into COS cells human hepatoma bFGF cDNA and a construct from which the AUG initiator was eliminated, it was found that the higher molecular mass forms of bFGF were as biologically active as the 18-kDa form.