Acute inflammatory response, neutrophils

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... 

The very early peak of neutrophil invasion into an inflamed area is followed several hours later by a wave of a second class of phagocytic cells, the macrophages. This biphasic pattern of inflammatory cell movement and accumulation is observed in most acute inflammatory responses. The mononuclear phagocyte in the blood is known as the monocyte and differentiates... 

Srikrishna, G., Toomre, D.K., Manzi, A., Panneerselvam, K., Freeze, H.H., Varki, A., and Varki, N.M. (2001) A novel anionic modification of N-glycans on mammalian endothelial cells is recognized by activated neutrophils and modulates acute inflammatory responses./. Immunol. 166, 624-632. 

Dietary copper deficiency increases the acute inflammatory response in rats and other small laboratory animals (Schuschke et al. 1994). The release of inflammatory mediators, such as histamine and serotonin, from mast cells increases the vascular permeability of postcapillary venules and results in edema. In copper-deficient rats, release of histamine from mast cells correlates positively with frequency of the acute inflammatory response. Copper-deficient rats (0.6 mg Cu/kg DW ration for 4 weeks) have more mast cells in muscle than copper-adequate controls given diets containing 6.3 mg Cu/kg DW ration however, histamine content of mast cells is not affected (Schuschke et al. 1994). An early clinical sign of copper deficiency is a reduction in the number of circulating neutrophils the mechanism for copper-deficient neutropenia (leukopenia in which... 

Several peptides (e.g., DITWDQLWDLMK) were found to inhibit E-selectin with values in the low nanomolar range and to block E-selectin-mediated adhesion to neutrophils in static and flowcell assays. In vivo experiments with an acute inflammatory response model in mice demonstrated that the best candidate was able to noticeably lower the extent of neutrophil transmigration to the site of inflammation. However, it was shown that the mechanism of action does not involve inhibition of E-selectin binding to sLe. ... 

However, the central paradox in our consideration of inflammatory disease is that the inflammatory response evolved as a highly effective component of the innate immune response of the body to infection or injury. Indeed, until the last two or three decades, inflammation was perceived as an entirely beneficial host response to injury or infection. Elias Metchnikoff, the fether of modern inflammatory cell biology, emphasized this concept in his work. Neutrophil and eosinophil granulocytes play key defensive roles in infections such as lobar streptococcal pneumonia and in parasitic infestations such as schistosomiasis. The acute inflammatory response in... 

Stimulation of cultured endothelial cells with thrombin, histamine, or H202 results in a rapid (within minutes) translocation of P-selectin (CD62P) to the cell surface from secretory granules known as Weibel-Palade bodies. In contrast, induction of endothelial E-selectin (CD62E) expression is dependent upon de novo synthesis following stimulation with cytokines such as IL-1 a and TNF-a.57 58 P- and E-selectin are only transiently expressed on the cell surface, during which time they bind to the sialylated Lewis X antigens of neutrophils and monocytes.59-61 Both selectins are implicated in leucocyte extravasation associated with the acute inflammatory response.62-63... 

Local downregulation of chemokine receptors on elicited neutrophils is probably an important mechanism for resolution of the acute inflammatory response. However, when intravascular neutrophils are prematurely activated, such as occurs during bacterial sepsis, the resulting downregulation of CXC chemokine receptors may render these cells unable to exit the vascular space... 

Pleurodesis is defined as the adherence of the visceral and parietal pleural surfaces with obliteration of their margins. Several agents are used as sclerotic agents to produce pleurodesis in patients with malignant pleural effusions, pneumothorax, and in rare cases of intractable pleural effusion (47). It appears that an acute inflammatory response mediated via interleukin-8 and MCP-1 is essential for the initiation of sclerosis (48). When talc was insufflated into the pleural space of 13 consecutive patients with spontaneous pneumothorax and eight patients with malignant pleural effusion, there was a rapid accumulation of neutrophils followed by mononuclear cells (49). The neutrophil influx correlated with the level of IL-8 in the pleural fluid however, the mononuclear cells did not appear to correlate with the level of MCP-1. 

Figure 1. Acute inflammatory response. Subsequent steps in neutrophil extravasation, movement toward the site of infection and removal of invading bacteria.

These are generated by the liver during infections and other forms of inflammatory challenge, as part of the acute-phase response. This response to infection is characterised by fever, sleep, adrenotrophic hormone release, decreased plasma iron and zinc levels, elevated neutrophils in the bloodstream and enhanced cytokine production. These changes, part of the body s response to combat infection, occur within hours. The elevated temperatures may inhibit the replication of some bacteria and viruses and may also enhance the function of some immune cells. 

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