Eosinophils are white blood cells that in humans are found in association with helminthic infections and various inflammatory disease processes. These cells contain a unique lysosomal peroxidase that oxidizes halides to generate highly reactive and toxic hypohalous acids. Although chloride is found in vivo at concentrations at least 1000-fold greater than those of other halides, human eosinophils did not preferentially oxidize chloride under physiologic conditions. Instead, eosinophils used bromide, a halide with a hitherto unknown function in humans, to generate a halogenating oxidant with characteristics similar, if not identical, to those of hypobromous acid. These results indicate that physiological concentrations of bromide arm human eosinophils with the ability to generate and release an unusual oxidant capable of destroying a wide range of prokaryotic and eukaryotic targets.

Triggered human neutrophils were able to maintain released elastase in an active form in the presence of purified alpha-lproteinase inhibitor (a-l-PI), serum or bronchoalveolar lavage fluid (BAL). The accumulation of free elastase activity was associated with a decrease in the ability of the a-l-PI to inhibit porcine pancreatic elastase, an increase in proteinase activity associated with a-2-mac*roglobulin, and the oxidation of a-l-PI to a molecule containing four methionine sulfoxide residues. Neutrophils used both hypochlorous acid and long-lived N-chloroamines to oxidize the a-l-PI, but hypochlorous acid was preferentially used for suppressing the activity of the antiproteinase over short distances whereas the N-chloroamines were effective even when the phagocytes and a-l-PI were physically separated. Sodium dodecyl sulfate-polyacryhamide gel electrophoresis of purified a-l-PI, serum, or BAL that had been incubated with triggered neutrophils revealed that the released neutrophil elastase was not complexed with the antiproteinase and that a portion of the a-l-PI had undergone proteolysis. These data suggest that the presence of free neutrophil elastase as well as inactive, oxidized,and proteolyzed a-l-PI in fluids recovered from inflammatory sites in vivo could be directly mediated by triggered neutrophils alone.

Abstract. Triggered neutrophils rapidly de-graded labeled matrices secreted by cultured, venous endothelial cells via a process dependent on elastase but not oxygen metabolites. In the presence of high concentrations of alpha-I-proteinase inhibitor, the ability of the stimulated neutrophil to solubilize the matrix was impaired. However, at lower concentrations of alpha-1-proteinase inhibitor the neutrophil could enhance the degradative potential of its released elastase by a H202-dependent process. Coincident with this increase in matrix damage, the stimulated neutrophil destroyed the elastase inhibitory activity of the alpha-1 -proteinase inhibitor via a catalase-inhibitable process. The ability of the triggered neutrophil to solubilize the matrix in the presence of alpha-l-proteinase inhibitor was unaffected by superoxide dismutase or hydroxyl radical scavengers but was markedly impaired by catalase, azide, or hypochlorous acid scavengers. We conclude that neutrophils can cooperatively use an oxidant with characteristics similar, if not identical, to hypochlorous acid and the lysosomal proteinase elastase to negate the protective effects of alphal-proteinase inhibitor in order to attack the subendothelial matnx.

The gonadotropin-releasing hormone (GnRH) agonist D-Ala 6 -des-Glyio-GnRH ethylamide (D-Ala analog) was used as ligand to study GnRH receptors in the pituitary and gonads during sexual maturation in the rat. The affinities of the GnRH receptor (Ka = 6.5 x 10 9 M" 1 ) were similar in all three tissues and did not change during maturation. Pituitary GnRH receptor concentration increased 2-fold in both sexes. Peak values occurred earlier (20 days) and were higher (720 ± 52 fmol/ mg protein) in females than in males (30 days; 594 ± 54 fmol/ mg). The changes in GnRH receptors followed a pattern similar to that of plasma FSH, though GnRH receptors were maximal 10 days after the FSH peak. The binding capacity of the gonadal GnRH receptors also changed with age, and was maximal on day 20 in females (271 ± 25 fmol/mg) before declining to a constant level by day 60 (139 ± 20 fmol/mg). In males, binding to testicular interstitial tissue was not detectable at 30 days of age but increased rapidly to 256 ± 13 fmol/mg by 40 days, before declining to a stable level at 60 days (160 ± 14 fm/mg). The parallel rise in plasma FSH and pituitary GnRH receptor concentrations suggest that both are mediated by increased hypothalamic secretion of GnRH. The highest concentrations of GnRH receptors in the pituitary was found at an age when pituitary responsiveness to GnRH is known to be maximal. This suggests that an increase in GnRH receptor numbers form an important part of the mechanisms involved in increasing pituitary responses to GnRH. While the factors involved in determining gonadal GnRH receptors are unknown, the observed changes in receptor concentration suggest that GnRH or a GnRH-like peptide may be involved in controlling steroidogenesis during sexual maturation. (Endocrinology 108: 1658, 1981) M ATURATIONAL changes in the hypothalamicpituitary axis resulting in increased gonadotropin-releasing hormone (GnRH) secretion are generally believed to be responsible for initiating sexual maturation in mammals. The exact mechanisms involved are complex and incompletely understood, but several facets of this process have been previously studied. Hypothalamic GnRH content increases steadily during the first 50-60 days of life (1-3). The pituitary content of LH and FSH also increases with age, though the time course is different between the sexes (4-7). The patterns of plasma LH, FSH, PRL, and gonadal steroid concentrations during sexual maturation in rats have also been documented in previous studies (8-15). In males, plasma FSH levels increase markedly to a peak at 30 days of age, whereas LH levels show little change but tend to increase gradually after 30 days. Plasma testosterone rises after 40 days of age (12, 16), the earlier exposure of the testis to FSH having enhanced testicular responsiveness to LH (17). In