Intercellular adhesion molecule-1 (ICAM1) is a ligand for lymphocyte-function associated (LFA) antigens. Bella et al. (1998) analyzed the structural features of the ICAM1 molecule that underlie its function
as a receptor for the major group of human rhinoviruses and as a ligand for LFA1.
Intercellular adhesion molecule-1 (ICAM-1) is considered to have a prominent role in monocyte/macrophage adhesion
events. ICAM-1 is a 90- to 114-kDa cell surface protein that promotes monocyte/macrophage adhesion through a variety
of ligands and exists in both membrane-bound and circulating forms . Expression of ICAM-1 is
induced by proinflammatory cytokines, including interleukin-1, tumor necrosis factor-, and interferon-gamma.
NCBI Summary:
This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by Rhinovirus as a receptor. [provided by RefSeq, Jul 2008]
Vigan P, et al 1997 reported that intercellular adhesion molecule-1 is expressed on human
granulosa cells and mediates their binding to lymphoid cells. To assess the presence of ICAM-1
messenger RNA, total RNA obtained from freshly aspirated GCs and GCs luteinized in culture
was reverse transcribed and then amplified using two oligonucleotide primers specific for the
human ICAM-1 gene. A single major DNA band of the expected size (943 bp) was obtained. The
identity of this material with the human ICAM-1 sequence was further confirmed by restriction
enzyme analysis. Surface ICAM-1 protein was detected by flow cytometric analysis on luteinized
GCs cultured for 7 and 15 days. Finally, to evaluate a possible functional activity of ICAM-1, a
51Cr-release-binding assay between peripheral blood lymphocytes and luteinized GCs was
performed in the presence and absence of a monoclonal antibody against ICAM-1. As a result,
lymphocyte adhesion to GC monolayers was significantly, but not completely, inhibited by the
anti-ICAM-1 monoclonal antibody.
Olson KK, et al reported prolactin-induced expression of intercellular adhesion
molecule-1 and the accumulation of monocytes/macrophages during
regression of the rat corpus luteum and
conclude that ICAM-1 expression and monocyte/macrophage accumulation
are associated with prolactin-induced luteal regression in the rat and that
these aspects are not influenced by testosterone.
Expression regulated by
Growth Factors/ cytokines, Eicosanoids, prolacin
Comment
TGF-β1 inhibits microvascular-like formation by decreasing VCAM1 and ICAM1 via the upregulation of SNAIL in human granulosa cells. Li H et al. (2021) Three major endothelial cell junctional adhesion molecules (VCAM1, ICAM1 and E-SELECTIN) play important roles in the process of angiogenesis, a progression of extensive physiological vascularization that occurs during the formation of the corpus luteum. Our previous studies demonstrated that TGF-β1 is a negative regulator of luteinization and progesterone production in luteinized human granulosa (hGL) cells. Whether TGF-β1 can regulate the expression of these endothelial cell adhesion molecules and subsequent angiogenesis in hGL cells remains to be elucidated. Using dual inhibition approaches (small molecular inhibitors and siRNA-based knockdown), we provided the first data showing that TGF-β1 significantly upregulates the expression of the SNAIL transcription factor, which in turn suppresses the expression of VCAM1 and ICAM1 in hGL cells. Additionally, we demonstrate that the suppressive effects on the expression of VCAM1 and ICAM1 induced by TGF-β1 treatment were most likely via an ALK5-mediated SMAD-dependent signaling pathway. Furthermore, functional studies showed that hGL cells cultured on Matrigel exhibited two typical endothelial cell phenotypes, microvascular-like formation and a sprouting microvascular pattern. Notably, these phenotypes were significantly suppressed by either TGF-β1 treatment or knockdown of VCAM1 and ICAM1. Our findings suggest that TGF-β1 plays a potential role in the inhibition of granulosa cell angiogenesis by downregulating the expression of VCAM1 and ICAM1 during follicular development and corpus luteum formation.//////////////////Olson KK, et al 2001 reported actions of prostaglandin F-2 alpha and prolactin on
intercellular adhesion molecule-1 expression and
monocyte/macrophage accumulation in the rat corpus luteum.
Expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation
of monocytes/macrophages are inflammatory events that occur during PRL
(PRL)-induced regression of the rat corpus luteum. Immature
rats were ovulated with eCG-hCG and then hypophysectomized (Day 0), which
resulted in a single cohort of persistent, functional corpora lutea. On Days
9-11, the rats received twice daily injections of saline, PGF (Lutalyse, 250
mug/injection), or PRL (312 mug/injection) to induce luteal regression.
Surprisingly, luteal weight and plasma progestin concentrations (progesterone
and 20 alpha -dihydroprogesterone) did not differ between PGF-treated rats and
controls; whereas both luteal weight and plasma progestins declined
significantly in PRL-treated rats. Furthermore, corpora lutea of PGF-treated
rats and controls contained relatively minimal ICAM-1 staining and few
monocytes/macrophages. In contrast, but as expected, corpora lutea of
PRL-treated rats stained intensely for ICAM-1 and contained numerous
monocytes/macrophages. These findings suggest that prolactin, not PGF, induces the
inflammatory events that accompany regression of the rat corpus luteum.
Ovarian localization
Granulosa, Theca, Luteal cells
Comment
Periovulatory Expression of Intercellular Adhesion Molecule-1 in the Rat Ovary.
Bonello N, et al .
Leukocytes, especially neutrophils and macrophages, traditional cellular regulators of the immune system, reside within the tissue architecture of the rodent and human ovary and dramatically increase in number, in response to gonadotropin, in the theca of preovulatory follicles. Evidence strongly suggests a modulatory role for leukocytes in ovarian tissue remodeling events, such as ovulation, luteinization and luteolysis. The present study investigates the ovarian localization and potential gonadotropin regulation of intercellular adhesion molecule-1 (ICAM-1), an important factor in neutrophil and monocyte attachment to endothelium. Reverse transcription-polymerase chain reaction and immunohistochemical detection and quantification of ICAM-1 mRNA and protein was carried out in ovaries of immature and eCG/hCG-primed rats during the periovulatory period (0,6,12 and 24h post-hCG). While whole ovarian ICAM-1 mRNA levels did not vary significantly during the preovulatory period, ovarian follicles exhibited ICAM-1 mRNA and protein specifically within the thecal region, where mRNA expression increased 5-fold and protein expression increased 6-fold when comparing pre-hCG levels with those at the estimated time of ovulation (12h post-hCG). Thecal ICAM-1 was most prevalent in highly vascularized regions as evidenced by serial staining with an endothelium-specific antibody. Granulosa layer ICAM-1 immunoactivity was acquired only during/after follicle rupture. These results show ICAM-1 is localized within the ovarian theca and its expression is associated with follicular development in periovulatory follicles, peaking in expression at the time of rupture. Additionally, ICAM-1 is expressed amongst granulosa-lutein cells of the ovulating follicle and developing corpus luteum. Taken together these findings suggest rat ovarian ICAM-1 may be instrumental in the active recruitment of leukocytes into the preovulatory ovary and may have a role in corpus luteum formation.
Follicle stages
Preovulatory, Corpus luteum
Comment
Vigan P, et al reported that soluble intercellular adhesion molecule-1 in ovarian
follicles: production by granulosa luteal cells and levels in follicular fluid.
Soluble ICAM-1 can be released by granulosa luteal cells and can be
detected in FF after ovarian hyperstimulation. Levels of soluble ICAM-1 in FF correlate directly
with some indices of ovarian function.
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Sligh et al. (1993) disrupted the gene in murine embryonic stem cells by
gene targeting. Homozygous deficient animals developed normally, were fertile, and had a moderate
granulocytosis. Studies were consistent with complete loss of surface expression of the protein. Deficient mice
exhibited prominent abnormalities of inflammatory responses including impaired neutrophil emigration in response
to chemical peritonitis and decreased contact hypersensitivity to 2,4-dinitrofluorobenzene.
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Association of TLR2 S450S and ICAM1 K469E polymorphisms with polycystic ovary syndrome (PCOS) and obesity. Ojeda-Ojeda M et al. (2015) Toll-like receptors (TLRs) are activated by inflammatory stimuli and influence endothelial functions, contributing to the pathogenesis of atherosclerosis. We investigate the influence of polymorphisms in the genes encoding toll-like receptor 2 (TLR2) and 4 (TLR4) and endothelial adhesion molecules on polycystic ovary syndrome (PCOS) and its interaction with obesity. Ten single nucleotide polymorphisms were genotyped in 305 women with PCOS and 166 non-hyperandrogenic control women. In obese women, TLR2 S450S and ICAM1 K469E polymorphisms differently influenced metabolic variables and PCOS, respectively. Irrespective of PCOS, variant alleles of TLR2 S450S increased triglycerides, fasting insulin levels, and insulin resistance in obese women. TLR2 S450S interacted with obesity and PCOS on androstenedione levels, mutant alleles were associated with increased androstenedione concentrations in all women, with the exception of obese patients with PCOS (P=0.034). Regarding ICAM1 K469E, homozygosis for K469 alleles was more frequent in PCOS, but only in obese women (P=0.014). K469 alleles were also related to increased body mass index (P=0.017) and diastolic blood pressure (P=0.034). Moreover, ICAM1 K469E interacted with obesity and PCOS on serum triglyceride levels (P=0.019) and with PCOS on serum sex hormone-binding globulin concentrations (P=0.006). In conclusion, TLR2 S450S and ICAM1 K469E polymorphisms may be associated with PCOS and metabolic comorbidities in obese women.//////////////////