Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 700

11.5.2.1 Pro-Inflammatory Cytokines Involved in Extravasation

Leukocyte extravasation is influenced by: (1) pro-inflammatory cytokines, such as
interleukins IL1

, among others, and (2) chemoattrac-
tants for myeloid cells, such as N formyl methionyl leucyl phenylalanine (fMLP),
complement component C5a, leukotriene LTb4, and platelet-activating factor, pro-
duced in the inflammatory site [ 1445 ].
The secretion of a selective set of chemokines and upregulated expression of
endothelial adhesion molecules caused by specific cytokines direct the subpopula-
tions of leukocytes that are recruited during different phases of inflammation. In
response to pro-inflammatory stimuli, such as TNF

α ,IL1 β , and IL6, and TNF α

, and thrombin,
endothelial cells synthesize different chemokines, such as CCL2, CCL5, CXCL1,
CXCL8, CXCL10, or CXCL12 [ 1445 ].
Endothelial cells produce chemokines attached to glycosaminoglycans and
Duffy receptor for chemokines, especially in apical endothelial microvilli [ 1445 ].
These endothelium-immobilized chemokines promote the transition from selectin-
mediated tethering and rolling of leukocytes to integrin-mediated firm attachment
and spreading, as they activate their cognate Gi/o-coupled chemokine receptors
to express leukocyte integrins. In addition, neutrophils secrete chemoattractants to
recruit other leukocyte types in later stages of inflammation.
During inflammation, myeloid cell subpopulations, in which several chemokine
receptors are upregulated, migrate from the bone marrow to inflammation loci and
uptake antigens. The innate immune response that involves monocytes, macro-
phages, and dendritic cells, occurs in the inflamed tissue. Migration of immature
dendritic cells to inflammation zones depends on the expression of chemokine
receptors such as CCR2, CCR5, and CCR6 [ 1445 ]. After antigen uptake, the density
of these chemokine receptors on mature dendritic cells decays, whereas CCR7
expression rises.
Conventional dendritic cells can then move via lymphatics to draining lymph
nodes. In lymph nodes, mature dendritic cells present antigens to specific naive
T cells. Naive T lymphocytes differentiate into effector (T H1 ,T H2 ,T H9 ,T H17 ,
T H22 , and follicular T cells) and regulatory T lymphocytes (Table 11.5 ). Effector
CD4

α ,IL1 β , Ifn γ

T cells, and NK cells upregulate chemokine
receptors to also migrate to inflammation sites and mount a specialized immune
response. In addition, Ly6c high 29

+ T cells, T Reg , cytotoxic CD8 +

30

Ly6g + monocytes migrate to participate in

mucosal immunity [ 1445 ].

29 Lymphocyte antigen-6 complex, locus C in rodents.
30 Lymphocyte antigen-6 complex, locus G in Mus musculus. Lymphocyte antigen-6 complex, loci
Ly6g5c, Ly6g6c, and Ly6g6d exist in humans, in addition to Ly6d and Ly6h.