Neutrophils apoptotic

In the very early phases of the acute inflammatory response most of the cells invading the damaged area are polymorphonuclear neutrophils, also denoted as PMNs, which serve as initial line of defense and source of proinflammatory cytokines. These cells, which usually live for 4-5 days, circulate in the blood until they are attracted by chemokines into injured tissues. Whereas physical injury does not recruit many neutrophils, infections with bacteria or fungi elicit a striking neutrophil response. The characteristic pus of a bacterial abscess is composed mainly of apoptotic (apoptosis) and necrotic PMNs. Emigration of neutrophils from the blood starts with a process denoted as margination where neutrophils come to lie at the periphery of flowing blood cells and adhere to endothelial cells (Fig. 1). L-Selectin is expressed... 

Numerous studies have demonstrated that degradation products of (3-carotene exhibit deleterious effects in cellular systems (Alija et al., 2004, 2006 Hurst et al., 2005 Salerno et al., 2005 Siems et al., 2003). A mixture of (3-carotene degradation products exerts pro-apoptotic effects and cytotoxicity to human neutrophils (Salerno et al., 2005 Siems et al., 2003), and enhances the geno-toxic effects of oxidative stress in primary rat hepatocytes (Alija et al., 2004, 2006), as well as dramatically reduces mitochondrial activity in a human leukaemic cell line, K562, and RPE 28 SV4 cell line derived from stably transformed fetal human retinal pigmented epithelial cells (Hurst et al., 2005). As a result of degradation or enzymatic cleavage of (3-carotene, retinoids are formed, which are powerful modulators of cell proliferation, differentiation, and apoptosis (Blomhoff and Blomhoff, 2006). 

Schagat, T.L., Wofford, J.A., and Wright, J.R., Surfactant protein A enhances alveolar macrophage phagocytosis of apoptotic neutrophils, J. Immunol. 166, 4, 2727, 2001. 

Aburatubolactam A (91) and C (92) were isolated from the culture broth of Streptomyces sp recovered from a mollusk. X-ray diffraction studies established the structure of aburatubolactam A which was reported to inhibit TPA-induced superoxide anion generation by human neutrophils [149]. Aburatubolactam C appears to be cytotoxic for various proliferating tumor cells of human and murine origin (0.3-5.8 ig/ml) via apoptotic DNA fragmentation [150,151]. 

TheTNF-a-dependent models are mostly characterized by the apoptotic cell death of hepatocy te at the early stage of liver injury. In these models, a large number of hepatocytes undergoing apoptosis can represent a stimulus for primed neutrophils in sinusoids to transmigrate and activate, leading to hepatic inflammation and massive hepatocyte necrosis. This... 

Socie G, Mary JY, Lemann M. 2004. Prognostic value of apoptotic cells and infiltrating neutrophils in graft-versus-host disease of the gastrointestinal tract in humans TNF and Fas expression. Blood. 103 50-57. 

Fig. 4. Acute MI with interstitial infiltration of neutrophil granulocytes. (A) Hematoxylin and eosin. (B) Immunohistochemical staining for activated caspase-3 positive reaction in numerous neutrophil granulocytes. Apoptotic bodies are also positive.

Cox G, Crossley J, Xing Z. Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo. Am J Respir Cell Mol Biol 1995 12 232-237. 

Gilligan HM, Bredy B, Brady HR, Hebert MJ, Slayter HS, Xu Y, Rauch J, Shia MA, Koh JS, Levine JS. Antineutrophil cytoplasmatic autoantibodies interact with primary granule constituents on the surface of apoptotic neutrophils in the absence of neutrophil priming. J Exp Med 1996 184 2231-2241. 

Yang JJ, Tuttle R,TaylorJG, Jennette JC, Falk RJ. ANC A target antigens are not on the surface of normal neutrophils but are present on both primed and apoptotic neutrophils. J Am Soc Nephrol 1997 8 546 (abstract). 

Flgure 12.1 Electron micrograph of an apoptotic human neutrophil showing the characteristic chromatin aggregation, prominent nucleolus and dilated cytoplasmic vacuoles. Note that the cell membrane is intact and the granule structure appears normal. (EM taken by Jan Henson), (x 11 000). 

Figure 12.2 The characteristic ladder pattern on agarose gel electophoresis of DNA extracted from apoptotic neutrophils. This cleavage of fragments which are integers of 180 kb is indicative of intemucleosomai cieavage.

The speed with which monocyte-derived macrophages recognize, ingest and destroy apoptotic neutrophils in vitro is quite remarkable. Individual macrophages can ingest several neutrophils (see Fig. 12.3), and once... 

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