Induction of cyclooxygenase-2 by human monocytes exposed to group B streptococci.

Group B streptococcal (GBS) infections are associated with high morbidity and mortality. The molecular pathways mediating the pathophysiological events in GBS infection are not fully delineated. Cyclooxygenases (COX) are the enzymes that convert arachidonate to active eicosanoids. To identify the effects of GBS on eicosanoid metabolism and regulatory mechanisms, we exposed human monocytes to GBS and found that they secreted prostaglandin E2, prostacyclin, and thromboxane A2. Exposure to GBS caused monocytes to express COX-2 mRNA and protein in both a time- and concentration-dependent manner that correlated with eicosanoid production. COX-1 protein was unchanged. Addition of the anti-inflammatory cytokines interleukin (IL)-4 or IL-10 markedly attenuated GBS-induced COX-2 protein accumulation after GBS exposure, as did inhibition of p38 MAPK. Our experiments are the first to show that exposure of monocytes to a gram-positive bacterium (GBS) results in induction of functional COX-2, suggesting that eicosanoids may play important roles in the pathogenesis of GBS infections.

Inflammatory agonists induce cyclooxygenase type 2 expression by human neutrophils.

The synthesis of prostanoids is regulated by cyclooxygenases (prostaglandin H synthases), which catalyze the conversion of arachidonic acid to PGH2. Cyclooxygenases are the target of aspirin and other nonsteroidal anti-inflammatory agents. In this study, we found that human polymorphonuclear leukocytes (PMNs) express the inducible isoform of cyclooxygenase, COX-2, when stimulated by LPS whereas the protein was not detectable in freshly isolated human PMNs. We also found by immunohistochemical analysis that COX-2 is expressed in PMNs in inflamed human tissues. COX-2 was induced in a time- and concentration-dependent fashion when isolated human PMNs were exposed to LPS; COX-2 was also induced, or its expression was increased, by TNF-alpha, IL-1, and IL-8. Expression of COX-2 in stimulated PMNs was paralleled by secretion of PGE2. The release of PGE2 was blocked by a selective nonsteroidal inhibitor of COX-2, indicating that the enzyme is responsible for the prostanoids produced, and was inhibited by dexamethasone. The time course of LPS-induced COX-2 expression and other features were different in freshly isolated PMNs, monocytes, and macrophages, indicating that COX-2 expression is differentially regulated in myeloid cells of different lineages and degrees of maturation. Consistent with this, IL-4 and IL-10, which suppressed LPS-induced COX-2 expression in monocytes, had little effect on this response by PMNs. These experiments demonstrate that PMNs express COX-2 when appropriately stimulated. Thus, they may actively influence the eicosanoid composition of the acute inflammatory milieu.

Temporal integration in two species of Old World monkeys: blue monkeys (Cercopithecus mitis) and grey-cheeked mangabeys (Cercocebus albigena).

Changes in auditory sensitivity as a function of signal duration were studied in two species of Old World monkeys. Testing was conducted under free-field conditions with pure tones 250, 800, 1600, and 4000 Hz in frequency. Test stimuli ranged in duration from 35-2000 ms. The results showed that the temporal integration functions for the blue monkeys were similar to those reported for rhesus monkeys [T. D. Clack, J. Acoust. Soc. Am. 40, 1140-1146 (1966)], but differed significantly from those for mangabey monkeys and human subjects tested in the same apparatus, by the same procedure. Integration functions for humans and mangabeys did not differ. It was concluded that some taxonomic groups of primates exhibit temporal integration times that are much longer than those characteristic of humans, while others do not, and that interspecific differences in temporal integration are not readily related to species differences in their vocal repertoires.