The American journal of physiology
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Reperfusion of acutely ischemic skeletal muscle is associated with neutrophil activation, which may augment local injury or cause damage to distant organs. Polymorphonuclear neutrophil glycoprotein CD18 plays a role in this injury, since its blockade substantially reduces damage; however, its mechanisms of control during reperfusion are poorly understood. The purpose of this study was to investigate the importance of circulating plasma factors to CD18-dependent neutrophil function during reperfusion and to relate these to quantitative expression of CD18. ⋯ CD18 expression increased only at 24 h and did not increase proportional to increases in adherence and oxidant production. Control plasma (nonischemic, n = 5) elicited no significant differences of any inflammatory measure during sham ischemia or reperfusion. These results indicate that endogenous mediators may evoke a progressive systemic inflammatory response after ischemia by stimulating CD18-dependent neutrophil function in a delayed but prolonged manner.
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The mechanism for neutrophil (PMN) influx into infected airspaces of the lung is not known. To determine whether alveolar macrophage products are important in the initiation of chemotaxis, we depleted rats of alveolar macrophages by aerosolizing negatively charged oligolamellar liposomes complexed to clodronate disodium. Ninety-five percent of the alveolar macrophages were depleted, and lung injury and inflammation were minimized with this depletion technique. ⋯ Levels of bioactive tumor necrosis factor-alpha and immunoreactive proteins CINC/gro (cytokine-induced PMN chemoattractant) in the lavage fluids obtained from infected rats depleted of alveolar macrophages were significantly decreased compared with the levels in the lavage fluids obtained from normal infected rats. MIP-2 mRNA expression, as detected by Northern analysis, was also decreased in the infected lungs of depleted rats, and the lavage fluid from these rats had significantly decreased chemotactic activity. Therefore these results suggest that alveolar macrophage products play a direct role in the initial recruitment of PMN into infected lungs.
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The purpose of this paper was to obtain probes to study the structure and function of mucins in rat models of airway cell differentiation and disease. We report the isolation and characterization of the rat cDNA homologue of the human airway secretory mucin, MUC5. Furthermore, we demonstrate the coordinate regulation of the expression of MUC5 and MUC1 (a membrane-bound mucin) and mucous differentiation. ⋯ Furthermore, neither mucin gene was expressed in retinoid-deficient cultures that undergo squamous instead of mucous differentiation. These studies demonstrate that expression of MUC1 and MUC5 is coordinately regulated with airway mucous cell differentiation. These cDNAs should provide useful tools to study mucin synthesis during differentiation and disease.
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Comparative Study
Opossum colonic mucosa contains uroguanylin and guanylin peptides.
Uroguanylin and guanylin are structurally related peptides that activate an intestinal form of membrane guanylate cyclase (GC-C). Guanylin was isolated from the intestine, but uroguanylin was isolated from urine, thus a tissue source for uroguanylin was sought. In these experiments, uroguanylin and guanylin were separated and purified independently from colonic mucosa and urine of opossums. ⋯ In contrast, colonic, urinary, and synthetic guanylin had an isoelectric point of approximately 6.0, eluted at 15-16% acetonitrile on C18 RP-HPLC columns, stimulated greater cGMP responses in T84 cells at pH 8 than pH 5.5, and were inactivated by chymotrypsin, which hydrolyzed the Phe-Ala or Try-Ala bonds within guanylin. Uroguanylin joins guanylin as an intestinal peptide that may participate in an intrinsic pathway for cGMP-mediated regulation of intestinal salt and water transport. Moreover, uroguanylin and guanylin in urine may be derived from the intestinal mucosa, thus implicating these peptides in an endocrine mechanism linking the intestine with the kidney.
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To clarify mechanisms of hypothermia in lipopolysaccharide (LPS) shock, four experiments were conducted in 72 chronically instrumented Wistar rats. They were intended to accomplish the following: experiment 1, determine the dose of intravenous Escherichia coli LPS that induces a body temperature (Tb) fall at a minimal mortality [the dose chosen (0.5 mg/kg) was then used in experiments 2-4]; experiment 2, identify the time course of the arterial blood pressure (BP) fall (shock) during the response to LPS; experiment 3, measure threshold Tb values for skin vasodilation and activation of metabolic heat production (M) during the LPS shock; and experiment 4, ascertain behavioral thermoregulation in LPS shock. For experiments 1-3, rats were kept in restrainers; ambient temperature (Ta) was 26 degrees C. ⋯ The major autonomic mechanism of the shock hypothermia was a shift in the threshold Thy for M from 37.9 +/- 0.3 to 36.0 +/- 0.3 degrees C (experiment 3; P < 0.05). In experiment 4, rats selected Tpr below 25 degrees C (vs. 28-30 degrees C in control; P < 0.05) throughout the duration of the shock; their Tb dropped to 36.2 +/- 0.3 degrees C (P < 0.05). In sum, the LPS shock-associated hypothermia involves a decrease in the threshold Tb for M, the resultant widening of the interthreshold zone, and cold-seeking behavior.