Neutrophil activation, pulmonary

The Hi Receptor and its Ligands. The H receptor mediates effects, through an increase in cyclic adenosine monophosphate (cAMP). such as gastric acid secretion relaxation of airway smooth muscle and of pulmonary vessels increased lower airway mucus secretion esophageal contraclion inhibition of basophil, but not mas cell histamine release inhibition of neutrophil activation and induction or suppressor T cells. There is no evidence that the H- receptor causes significant modulation of lung function in the healthy human subject or in the asthmatic. 

May GR, Crook P, Moore PK, Page CP (1991) The role ofnitric oxide as an endogenous regulator of platdet and neutrophil activation within the pulmonary drculation Br J Pharmacol 102 759-763. 

Whatever the truth of the matter, G-CSF should be regarded as a possible cause of pulmonary complications. The abrupt increase in the number of activated neutrophils after G-CSF may account for exacerbation of latent chemotherapy-induced pulmonary damage. Endothelial damage subsequent to increased neutrophil activity (that is, enhanced superoxide release and increased adhesion molecule expression and adherence) or the release of cytokines (IL-1, IL-6, TNF) has been advanced as possible mechanisms. In addition, transient slight hypoxia was found in G-CSF users, although no relation with specific cytotoxic drug treatment or previous radiotherapy was identified (32). A sudden increase in neutrophil count, a rise in LDH and C reactive protein, and the occurrence of dyspnea or fever in G-CSF-treated patients were proposed as possible early signs of the subsequent development of interstitial pneumonia. 

Two major but conflicting hypotheses have been proposed to explain the connection between abnormal CFTR activity in cystic fibrosis and the chronic neutrophil-dominated pulmonary inflammation and colonization with common bacteria. These hypotheses have been referred to as the high-salt hypothesis proposed by Michael Welsh and his colleagues at the University of Iowa, and the reduced pericellular volume hypothesis proposed by Richard Boucher and colleagues at the University of North Carolina. 

Jones HA, Schofield JB, Krauss T, Boobis AR, Hasleft C. Pulmonary fibrosis correlates with the duration of tissue neutrophil activation. Am J Respir Crit Care 1998 158 620-628. 

Planaguma, A., Domenech, T., Pont, M., Calama, E., Garcia-Gonzalez, V., Lopez, R., et al. (2015). Combined anti CXC receptors 1 and 2 therapy is a promising antiinflammatory treatment for respiratory diseases by reducing neutrophil migration and activation. Pulmonary Pharmacology Therapeutics, 34, 37—45. http //dx.doi.org/ 10.1016/j.pupt.2015.08.002. 

Cohen, A. B., Stevens, M. D., Miller, E. J., Atkinson, M. A., Mullenbach, G-, Maunder, R. J., Martin, T. R., Wiener-Kronish, J. P., and Matthay, M. A. (1993) Neutrophil-activating peptide-2 in patients with pulmonary edema from congestive heart failure or ARDS. Am. J. Physiol. 264, L490-L495. 

Jones HA, Clark JC, Minhas PS, Kendall IV, Downey SP, Menon DK. Pulmonary neutrophil activation following head trauma [abstract]. Am J Respir Crit Care Med 1998 157 A349. 

Phon, S.H., Gannon, D.E., Varan, J., Ryan, V.S. and Ward, P.A. (1989). Xanthine oxidase activity in rat pulmonary artery endothelial cells and its alteration by activated neutrophils. Am. J. Path. 134, 1201-1211. 

Figure 5. Pulmonary inflammatory response to chronic diesel exhaust exposure as measured in bronchoalveolar lavage fluid. The total amount or activity of material removed from the lung has been normalized to the weight of control lungs. Inflammatory response is indicated by influx of neutrophils (PMN). Cytotoxicity is indicated by extracellular lactate dehydrogenase (LDH). (Continued on next page.)...

High antioxidative activity carvedilol has been shown in isolated rat heart mitochondria [297] and in the protection against myocardial injury in postischemic rat hearts [281]. Carvedilol also preserved tissue GSL content and diminished peroxynitrite-induced tissue injury in hypercholesterolemic rabbits [298]. Habon et al. [299] showed that carvedilol significantly decreased the ischemia-reperfusion-stimulated free radical formation and lipid peroxidation in rat hearts. Very small I50 values have been obtained for the metabolite of carvedilol SB 211475 in the iron-ascorbate-initiated lipid peroxidation of brain homogenate (0.28 pmol D1), mouse macrophage-stimulated LDL oxidation (0.043 pmol I 1), the hydroxyl-initiated lipid peroxidation of bovine pulmonary artery endothelial cells (0.15 pmol U1), the cell damage measured by LDL release (0.16 pmol l-1), and the promotion of cell survival (0.13 pmol l-1) [300]. SB 211475 also inhibited superoxide production by PMA-stimulated human neutrophils. 

The most common etiology is exposure to environmental tobacco smoke, but other chronic inhalational exposures can also lead to COPD. Inhalation of noxious particles and gases stimulates the activation of neutrophils, macrophages, and CD8+ lymphocytes, which release a variety of chemical mediators, including tumor necrosis factor-a, interleukin-8, and leukotriene B4. These inflammatory cells and mediators lead to widespread destructive changes in the airways, pulmonary vasculature, and lung parenchyma. 

The increased expression of adhesion molecules by the endothelium may activate polymorphonuclear neutrophils (PMN) in rabbits [72], During endotoxic shock, activated PMNs release their granule content and secrete both proinflammatory and cytotoxic molecules. Pickaver et al. [73] were the first to show PMN cytotoxicity against tumor cells. We showed that PMNs are toxic for PROb colon tumor cells [74] in BDEX rats. In vivo, PMNs have been implicated in the Schwartzman reaction [75], and may be involved in LPS-induced tumor necrosis. PMNs, when activated by LPS, synthesize and release NO. The role of NO in tumor growth will be discussed later. The decrease in tumor growth after intradermal injections of LPS is attributed to the induction of TNF-a secretion by PMNs both in intradermal tumors (Meth A sarcoma in BALB/c mice, MH-134 hepatoma in C3H/He mice, Lewis Lung carcinomas in C57BL/6 mice) and pulmonary Meth A metastases [76,77],... 

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