Inflammation vascular phase

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

In sensitized asthmatic individuals, antigen challenge generally causes a Type I (IgE-mediated) immediate hypersensitivity response by release of preformed mediators, including histamine, and prostaglandins, which are responsible for bronchoconstric-tion and increased vascular permeability. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hyper-secretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is driven by leukotrienes, chemokines and cytokines synthesized by activated mast cells and Th2 cells. Both proteins and haptens have been associated with these types of reactions. 

Figure 15-4 In silico subtraction method for mechanistic study to compare the hepatic gene expression profile induced by compound X to other compounds that induce hepatic APR secondary to inflammation at sites other than the liver. In the proposed simple model, compound X-induced gene expression change has two components. One is vasculitis specific the other is acute phase response (APR) specific. By subtracting the APR specific component, we might select candidate genes that are specifically associated with the hepatic vascular lesion Diclofenac known to induce APR without triggering vasculitis in liver is used to subtract genes activated by hepatic APR from the compound X response.

There are a number of nonspecific laboratory tests that are useful to support the diagnosis of infection. The inflammatory process initiated by an infection sets up a complex of host responses. Activation of complements, such as C3a and C5a, initiates inflammation and sets off a cascade of changes and the subsequent release of mediators, all of which can be measured and monitored. Serum complement concentrations, particularly C3, usually are consumed as part of the host defense mechanism and subsequently are reduced during the early stages of an acute infectious process. Acute-phase reactants, such as the erythrocyte sedimentation rate (ESR) and the C-reactive protein concentration, are elevated in the presence of an inflammatory process but do not confirm the presence of infection because they are often elevated in noninfectious conditions, such as collagen-vascular diseases and arthritis. Large elevations in ESR are associated with infections such as endocarditis, osteomyelitis, and intraabdominal infections. ... 

The inflammation phase ( 0-6 days postwounding) involves increased vascular permeability and chemotaxis of cells from the surrounding tissues into the wound. Release of cytokines and growth factors takes place and cell migration is activated... 

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