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chemoattractant 164 chemotactic factor
(5-amino-2,3-dihydro-1,4-phthalazinedione). This is a
mechanism to measure the respiratory burst in phagocytes.
The oxidation of luminol increases intracellular luminescence.
Chronic granulomatous disease may be diagnosed by
this technique.
chemoattractant
A substance that attracts leukocytes and may induce significant
physiologic alterations in cells that express receptors
for them.
chemokine autoantibodies
Autoantibodies against members of the chemokine family
that include macrophage inflammatory proteins (MIPs)
MIP-1-α (stem-cell inhibitor), MIP-1-β, MIP-2-α (GRO-β),
GRO-α, MIP-2-α (GRO-γ); platelet factor-4 (PF-4);
interleukin-8 (IL8); macrophage chemotactic and activating
factor, IP-10; monocyte chemoattractant protein-1
(MCP-1); and RANTES. MCP-1, MIP-1, and RANTES are
the mononuclear cell chemoattractant equivalent of IL8. All
these molecules are able to stimulate leukocyte movement
(chemokinesis) and directed movement (chemotaxis). IL8,
the best known member of this subfamily, is a proinflammatory
cytokine synthesized by various cells that act as
neutrophil activators and chemotactic factors. It is believed
to be responsible for the induction and maintenance of
localized inflammation. Monoclonal antibodies against
IL8 and MCP-1 receptors can distinguish between MCP-1-
and IL8-responsive T lymphocyte subsets. The enzyme
immunoassay (EIA) technique is the preferred method for
assaying chemokines and chemokine autoantibodies.
chemokine receptor-like 1
A member of the G protein-coupled receptor family, the
chemokine receptor branch of the rhodopsin family. It is
expressed on neutrophils and monocytes but not on eosinophils.
It may be found in brain, placenta, lung, liver and
pancreas.
chemokine receptor
Cell surface molecules that transduce signals stimulating
leukocyte migration following the binding of the homologous
chemokine. These receptors belong to the seventransmembrane
and α-helical, G protein-linked family.
Examples include Th1 cells that manifest CCR1, CCR5,
and CXCR3, which usher cells to sites of tissue inflammation;
Th2 cells bearing CCR4, CCR3, and CCR8, which
direct cells to mucosae; and naïve lymphocytes that bear
CR7, which guides cells to lymph nodes.
chemokines
Molecules that recruit and activate leukocytes and other cells
at sites of inflammation. They exhibit both chemoattractant
and cytokine properties. There are two groups. Those that
mainly activate neutrophils are the α chemokines (CXC
chemokines). By contrast, those that activate monocytes,
lymphocytes, basophils, and eosinophils are designated β
chemokines (CC chemokines). Blocking chemokine function
can exert a major effect on inflammatory responses.
chemokinesis
Determination of the rate of movement or random motion
of cells by chemical substances in the environment. The
direction of cellular migration is determined by chemotaxis,
not chemokinesis.
chemotactic assays
The chemotactic properties of various substances can be
determined by various methods. The most popular is the
Boyden technique, which consists of a chamber separated
into two compartments by a Millipore filter of appropriate
porosity through which cells can migrate actively but
not drop passively. The cell preparation is placed in the
upper compartment of the chamber, and the assay solution
is placed in the lower compartment. The chamber is
incubated in air at 37°C for 3 hours, after which the filter is
removed and the number of cells migrating to the opposite
surface of the filter are counted.
chemotactic deactivation
The reduced chemotactic responsiveness to a chemotactic
agent caused by prior incubation of leukocytes with the
same agent, but in the absence of a concentration gradient.
It can be tested by adding first the chemotactic factor to
the upper chamber, washing, and then testing the response
to the chemotactic factor placed in the lower chamber (no
gradient being present). The mechanism of deactivation has
been postulated as obstruction of the membrane channels
involved in cation fluxes. Deactivation phenomena are used
to discriminate between chemokinetic factors that enhance
random migration and true chemotactic factors that cause
directed migration. Only true chemotactic factors are able
to induce deactivation.
chemotactic disorder
Condition attributable to abnormalities of the complex
molecular and cellular interactions involved in mobilizing
an appropriate phagocytic cell response to injuries or
inflammation. It can involve defects in either the humoral
or cellular components of chemotaxis that usually lead to
recurrent infections. The process begins with the generation
of chemoattractants. Among these chemoattractants
that act in vivo are the anaphylatoxins (C3a, C4a, and C5a),
leukotriene B 4 (LTB 4), interleukin-8 (IL8), granulocyte–
macrophage colony-stimulating factor (GM-CSF), and
platelet-activating factors (PAFs). Once exposed to the
chemoattractant, circulating neutrophils embark upon a
four-stage mechanism of emigration through the endothelial
layer to a site of tissue injury where phagocytosis
takes place. The four stages include: (1) rolling or initial
margination by the selectins (L-, P-, E-); (2) stopping
on the endothelium by CD18 integrins and ICAM-1; (3)
neutrophil–neutrophil adhesion by CD11b/CD18; and (4)
transendothelial migration by CD11b/CD18, CD11a/CD18,
and ICAM-1. Chemotactic defects can be either acquired or
inherited. Specific disorders are listed separately.
chemotactic factor
Directed migration of cells, known as chemotaxis, is mediated
principally by the complement components C5a and
C5a–des Arg. Neutrophil chemoattractants also include
bacterial products such as N-formyl methionyl peptides,
fibrinolysis products, oxidized lipids such as leukotriene B 4,
and stimulated leukocyte products. Interleukin-8 (IL8) is
chemotactic for polymorphonuclear neutrophils (PMNs).
Chemokines that are chemotactic for PMNs include epithelial-cell-derived
neutrophil-activating peptide (ENA-78),
neutrophil-activating peptide 2 (NAP-2), growth-related
oncogene (GRO-α, β, and γ), and macrophage inflammatory
proteins 2α and β (MIP-2α and MIP-2β). Polypeptides
with chemotactic activity mainly for mononuclear cells (β
chemokines) include monocyte chemoattractant proteins 1, 2,
and 3 (MCP-1, MCP-2, and MCP-3), macrophage inflammatory
proteins 1α and β (MIP-1α and MIP-1β), and RANTES.