Basophil infiltration

Morbilliform exanthema, fixed drug eruptions, and erythrodermia are thought to result from a cell-mediated reaction, i.e., T-lymphocytes as in contact sensitivity. However, the histologic pictures of both reactions differ in a number of features. Moreover, basophil infiltration, which is rather important in contact sensitivity, is often negligible in the tuberculin reaction. In spite of several differences between... 

Parasympathetic reflexes may also regulate mediator release and lymphocyte activity (41). Furthermore, contralateral histamine release and basophil infiltration occur following ipsilateral nasal challenge with allergen (30), an event mediated by neural reflexes. 

In spite of the above-mentioned similarities between basophils and mast cells, they differ in many other aspects [1,2]. Basophils complete their differentiation within the bone marrow, and mature basophils circulate in the peripheral blood and do not usually infiltrate into peripheral tissues unless inflammation takes place. Mast cells originate from hematopoietic cells in the bone marrow as do basophils, but they mature in peripheral tissues after their bone marrow-derived precursors enter the circulation and migrate into peripheral tissues. Mature mast cells reside in peripheral tissues and do not usually circulate in the peripheral blood. The lifespan of basophils is very short (several days), in contrast to that of mast cells (weeks to months). Basophils do not proliferate once they terminally differentiate whereas mature mast cells keep potential to expand in response to various stimuli. These differences between basophils and mast cells, including distinct anatomical localization, suggest their differential roles in vivo. 

IL-4 which is a strong inducer of a type 2 cytokine milieu itself is produced by early skin-infiltrating T cells but it may also be released from mast cells, basophils or eosinophils during the acute eczematous skin reaction. Of note, the high frequency of IL-4-producing T cells in the skin is not necessarily associated with atopy since mRNA for IL-4 and T cells expressing IL-4 are found in nickel-induced patch test reactions as well. 

Cardiovascular In rodents, lymphohistiocytic infiltrates have been observed in the heart and in the perivascular space in various organs. Tissue macrophages in the heart can contain basophilic granules. In monkeys, no changes in ECG, heart rate, or blood pressure have been observed with numerous oligonucleotides. Under conditions when complement is activated, changes in blood pressure and cardiovascular collapse due to hypotension have been observed [55], but we have shown this to be related to complement activation rather than a direct effect on the cardiovascular system. (Of course, other mechanisms for hypotension could occur with other chemistries. For example, if an oligonucleotide formulation or its metabolic products chelates calcium, reductions in ionizable calcium could also produce a hypotensive crisis.) For most PS ODNs the most likely cause of hypotension is complement activation as demonstrated with complement inhibitors. 

When an antigen to which a normal patient has been exposed previously is injected into the skin, the area of the injection becomes infiltrated with lymphocytes within a few hours. In the next stage, additional lymphocytes and phagocytes (e.g., macrophages, neutrophils) infiltrate. The maximal intensity of the inflammatory reaction occurs by 24 to 72 hours. This reaction is often referred to as type FVhypersensitivity (i.e., cell-mediated see Chap. 86). In type I hypersensitivity, a positive skin reaction is evident usually within 15 minutes and always within 24 hours. Type I hypersensitivity involves the release of histamine from basophils and mast cells when antigen binds to the IgE on the surfaces of these cells. 

In general, CXC chemokines are attractants for neutrophils and T lymphocytes and ELR-CXC chemokines are attractants for B and T lymphocytes (Table 6.1). CC chemokines induce chemotaxis of multiple subsets of white blood cells, such as monocytes, basophils, dendritic cells, macrophages, NK cells and Tcells (Table 6.2). C chemokines are important for T cells traveling to the thymus and the CX3C chemokine, fractalkine, also acting as an adhesion molecule, seems to be important for the infiltration of T cells, NK cells and monocytes (Table 6.3). 

Blockade of CCR3 represents a new therapeutic target to inhibit eosinophil accumulation in vivo and will be a valuable tool to ascertain the effects of eosinophil infiltration on airway function and also to determine the role of eotaxin in recruiting basophils and Th2 lymphocytes, which also express CCR3, in allergic inflammation. 

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