Integrin expression in cells of the intervertebral disc

In this study, we investigated the profile of integrin expression in human and porcine intervertebral disc tissue. Differences in extracellular matrix composition between anulus fibrosus (AF) and nucleus pulposus (NP) regions of the disc, as well as differences in cellular responses to environmental stimuli, suggest a role for integrins in presenting matrix signals that may mediate these responses. Human disc tissue and porcine AF and NP tissue were stained with antibodies to alpha integrin subunits 1-6, V and IIb, and beta integrin subunits 1-6 and graded for evidence of positive staining on a scale from 0 (no staining) to 3 (high incidence of staining). Human tissue expressed alpha and beta integrin subunits shown to be present in articular cartilage, including alpha(1), alpha(5) and alpha(V). Porcine AF tissue expressed similar integrin subunits to human disc, with both expressing alpha(1), alpha(5), beta(1), beta(3) and beta(5) subunits, whereas porcine NP tissue expressed higher levels of alpha(6), beta(1) and beta(4) than AF tissue. The expressed subunits are known to interact with proteins including collagens, fibronectin and laminin; however, additional studies will be required to characterize the interactions of the integrin subunits with specific matrix constituents, as well as their specific involvement in regulating environmental stimuli.     

Expression of epithelial adhesion proteins and integrins in chronic inflammation.

Epithelial cell behavior in chronic inflammation is poorly characterized. During inflammation of tooth-supporting structures (periodontal disease), increased proliferation of epithelial cells into the inflamed connective tissue stroma is commonly seen. In some areas ulceration and degeneration take place. We studied alterations in the expression of adhesion molecules and integrins during chronic periodontal inflammation. In inflamed tissue, laminin-1 and type IV collagen were still present in the basement membrane and surrounding blood vessels, but they were also found extravascularly in inflamed connective tissue stroma. Type VII collagen and laminin-5 (also known as kalinin, epiligrin, or nicein) were poorly preserved in the basement membrane zone, but both were found in unusual streak-like distributions in the subepithelial connective tissue stroma in inflamed tissue. Both fibronectin and tenascin were substantially decreased in chronically inflamed connective tissue, showing only punctate staining at the basement membrane zone. Integrins of the beta 1 family showed two distinct staining patterns in epithelial cells during chronic inflammation; focal losses of beta 1 integrins (alpha 2 beta 1 and alpha 3 beta 1) were found in most areas, while in other areas the entire pocket epithelium was found to be strongly positive for beta 1 integrins. No members of the alpha v integrin family were found in any epithelia studied. Expression of the alpha 6 beta 4 integrin was high in basal cells of healthy tissue, but weak in epithelium associated with chronic inflammation. Chronic inflammation therefore involves alterations in both adhesion proteins and integrins expressed by epithelial cells. Basement membrane components found at abnormal sites in stroma in chronic inflammation might serve as new adhesive ligands for various cell types in inflamed stroma.     

Leukemia inhibitory factor (LIF) is immunohistochemically localized in tubal ectopic pregnancy

Leukemia inhibitory factor (LIF) is essential for implantation of the embryo in the endometrium. It is not clear whether the blastocyst requires expression of LIF for implantation into tissues other than endometrium. Immunohistochemical localization of LIF was performed in the fallopian tube of 20 women with ectopic pregnancies, 7 women with normal pregnancies and 20 healthy non-pregnant women. Fallopian tubes were evaluated from specimens taken during tubal ligation in normal pregnancies and non-pregnant fertile women or at operation for tubal surgery in ectopic pregnancies. Biopsies were assayed by immunohistochemistry. Semi-quantitative immunohistochemical reaction scores (IRS) were used for immunohistochemical analyses. Immunolabeling of LIF was detected in the surface epithelium and stroma of fallopian tubes in all subjects. IRS score in the epithelium and stroma of non-pregnant women and women with intrauterine pregnancy were similar (p>0.05). However, women with ectopic pregnancy had significantly increased labeling of LIF compared to others (p<0.05). Immunohistochemical labeling of LIF in the fallopian tube was found to be increased in ectopic pregnancies compared to non-pregnant and healthy pregnant controls. This may indicate a role of LIF in the ectopic implantation of embryos.     

Synthesis of African swine fever (ASF) virus-specific antibodies in vitro in a porcine leucocyte system.

The expression of HLA class II antigens by human fallopian tube epithelium was investigated in ectopic tubal pregnancy, in normal early and full-term intrauterine pregnancy, and during the menstrual cycle. Monoclonal antibodies directed against non-polymorphic (DA6.231, CR3/43, B7/21) and polymorphic (DA6.147, DA6.164, anti-leu-10) determinants of the HLA-D locus were used in a standard indirect immunoperoxidase method on fresh cryostat sections of fallopian tube. In ectopic pregnancy the tube epithelium showed uniform, intense reactivity for DR, DP and DQ. A similar reaction pattern was observed in normal first-trimester pregnancy. At term, most epithelial cells were DR-, DP- and DQ-positive, but a few were DP- and DQ-negative. In fallopian tubes from non-pregnant individuals, a variable number of epithelial cells labelled for DR alpha and DR beta but there was essentially no reactivity for DP or DQ. These results suggest differential regulation of class II MHC gene expression by tube epithelial cells, possibly mediated by hormones and/or a trophoblast product.     

Defective integrin switch and matrix composition at alpha 7-deficient myotendinous junctions precede the onset of muscular dystrophy in mice

Force transmission at the myotendinous junction requires a strong link between the muscle cytoskeleton and the extracellular matrix. At the adult junction, two splice variants of the laminin-binding integrins, alpha7Abeta1D and alpha7Bbeta1D, are highly enriched. The alpha7 subunits are critical for the integrity of the junctional sarcolemma because integrin alpha7-deficient mice develop muscular dystrophy, primarily affecting this site of the muscle. Here, we report that beta1D integrin coimmunoprecipitates and colocalizes with the alpha5 subunit at alpha7-deficient junctions, but does not associate with alpha3, alpha6 or alphav integrins. By immunogold labelling we show that the basement membranes of integrin alpha7-deficient muscles recruit abnormally high levels of fibronectin, the ligand of alpha5beta1D. Finally, we demonstrate that alpha5beta1D is down-regulated at the normal postnatal junction and is displaced by alpha7beta1D. These results suggest that the alpha7 subunit is implicated in the down-regulation of alpha5beta1D and in the removal of fibronectin from the maturing myotendinous junction, thus providing an alpha7beta1D-based link to laminin. We propose that the persistence of alpha5beta1D in alpha7-deficient mice is not compatible with normal muscle function and leads to muscle wasting.     

Targeted disruption of fibronectin-integrin interactions in human gingival fibroblasts by the RI protease of Porphyromonas gingivalis W50

Cell surface integrins mediate interactions between cells and their extracellular matrix and are frequently exploited by a range of bacterial pathogens to facilitate adherence and/or invasion. In this study we examined the effects of Porphyromonas gingivalis proteases on human gingival fibroblast (HGF) integrins and their fibronectin matrix. Culture supernatant from the virulent strain W50 caused considerably greater loss of the beta1 integrin subunit from HGF in vitro than did that of the beige-pigmented strain W50/BE1. Prior treatment of the W50 culture supernatant with the protease inhibitor Nalpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) blocked its effects on cultured cells, indicating that this process is proteolytically mediated. Purified arginine-specific proteases from P. gingivalis W50 were able to mimic the effects of the whole-culture supernatant on loss of beta1 integrin expression. However purified RI, an alpha/beta heterodimer in which the catalytic chain is associated with an adhesin chain, was 12 times more active than RIA, the catalytic monomer, in causing loss of the alpha5beta1 integrin (fibronectin receptor) from HGF. No effect was observed on the alphaVbeta3 integrin (vitronectin receptor). The sites of action of RI and RIA were investigated in cells exposed to proteases pretreated with TLCK to inactivate the catalytic component. Use of both monoclonal antibody 1A1, which recognizes only the adhesin chain of RI, and a rabbit antibody against P. gingivalis whole cells indicated localization of RI on the fibroblasts in a clear, linear pattern typical of that seen with fibronectin and alpha5beta1 integrin. Exact colocalization of RI with fibronectin and its alpha5beta1 receptor was confirmed by double labeling and multiple-exposure photomicroscopy. In contrast, RIA bound to fibroblasts in a weak, patchy manner, showing only fine linear or granular staining. It is concluded that the adhesin component of RI targets the P. gingivalis arginine-protease to sites of fibronectin deposition on HGF, contributing to the rapid loss of both fibronectin and its main alpha5beta1 integrin receptor. Given the importance of integrin-ligand interactions in fibroblast function, their targeted disruption by RI may represent a novel mechanism of damage in periodontal disease.     

Altered integrin expression in adenocarcinoma of the breast. Analysis by in situ hybridization.

The integrin superfamily of adhesion receptors mediates interactions between cells and the extracellular matrix. Our earlier immunohistochemical analysis showed that normal mammary epithelium expressed high levels of the alpha 2 beta 1 collagen/laminin receptor and intermediate levels of the alpha 5 beta 1 fibronectin receptor. In contrast, malignant cells of adenocarcinoma of the breast exhibited marked diminution or loss of the alpha 2 beta 1 and alpha 5 beta 1 integrins. We have now evaluated the level of alpha 2, alpha 5, and beta 1 integrin subunit messenger (m)RNA by in situ hybridization in adenocarcinoma of the breast. Normal breast ducts and ductules expressed high levels of all three integrin subunit mRNAs. Poorly differentiated lesions expressed low to undetectable levels of alpha 2, alpha 5, and beta 1 mRNA. Well- and moderately differentiated lesions expressed all three subunits at intermediate levels. Thus, decreased expression of the alpha 2 beta 1 and alpha 5 beta 1 integrins in mammary carcinoma is the result of decreased steady-state integrin subunit mRNA levels due to altered expression of the integrin genes.     

Hydrosalpinges adversely affect markers of endometrial receptivity

While in-vitro fertilization (IVF) was initially developed in women with tubal factor infertility, recent clinical studies have suggested that the presence of hydrosalpinges lowers implantation and pregnancy rates. We postulated that these hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with hydrosalpinges were prospectively evaluated, and compared with 55 infertile and 44 fertile controls. All women had endometrial biopsies during the window of implantation, analysed by conventional histological criteria, and also stained for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less of the alpha vbeta3 integrin compared with controls. There was no difference in expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater number of cases had out of phase histology and missing alpha vbeta3 (type I defects) and absent integrin expression despite normal histological maturation (type II) defects, compared with controls. Of 20 women with impaired endometrial receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of type II defects were corrected postoperatively. Using markers of endometrial receptivity, this study demonstrates that inflammatory hydrosalpinges have an adverse effect on endometrial receptivity, which in some cases may be overcome by surgical treatment of the hydrosalpinx.      

Co-ordinate expression of the alpha-6 integrin laminin receptor sub-unit and laminin in breast cancer.

Interactions between cells and extracellular matrices are mediated in part by a family of heterodimeric molecules known as integrins. We have investigated, using immunohistology, the distribution of six integrin alpha sub-units in normal breast tissue and 26 breast carcinomas. Alpha-1 integrin (collagen/laminin receptor sub-unit) was detected in myoepithelium, but not in luminal epithelium nor in most (20/26) carcinomas. Its expression on fibroblasts was enhanced in desmoplastic stroma. Both benign and malignant epithelium showed uniform positive staining for alpha-2 (collagen receptor sub-unit) and for alpha-3 (collagen/fibronectin/laminin receptor sub-unit). All epithelium was negative for alpha-4 (sub-unit of a fibronectin receptor). Epithelial staining for alpha-5 (fibronectin receptor sub-unit) was weak in all samples. Alpha-6 (sub-unit of two integrin laminin receptors) showed conspicuous changes in all invasive carcinomas. In normal tissues, there was weak staining of epithelial cytoplasm with alpha-6 antibody and moderate cell membrane staining. Strongest staining was present in a basement membrane distribution. In carcinomas, loss of cytoplasmic and cell membrane staining was variable, but basal membrane staining was diminished or absent in all tumours. Loss of basal membrane staining for alpha-6 integrin corresponded closely to loss of immunoreactivity for its ligand laminin in invasive breast cancer.     

Clomiphene citrate does not affect the secretion of alpha3, alphaV and beta1 integrin molecules during the implantation window in patients with unexplained infertility.

BACKGROUND: The expression of integrin molecules on the endometrium suggests that certain integrins may participate in the cascade of molecular events leading to successful implantation. A prospective, controlled study was carried out to investigate the effect of clomiphene citrate (CC) on secretions of beta1, alpha3 and alphaV integrin molecules in the endometrium of patients with unexplained infertility during the implantation window. METHODS: A total of 40 endometrial samples was evaluated in both spontaneous (n = 13) and ensuing clomiphene-treated cycles (100 mg on days 5-9) and also from fertile women serving as controls (n = 14) during postovulatory 7th or 8th day of menstrual cycle. A semiquantitative grading system (H-score) was used to compare the immunohistochemical staining intensities. Endometrial thickness and serum oestradiol and progesterone concentrations were also measured on the day of sampling. RESULTS: Staining of alpha(v) but not beta1 and alpha3 integrins was significantly less intense in infertile cases than fertile control cases (1.42 +/- 0.12 versus 2.21 +/- 0.13 respectively, P = 0.012) and this was not restored to normal concentrations with treatment. CONCLUSIONS: Our study indicated that cc treatment significantly decreased the endometrial thickness and increased oestradiol and progesterone concentrations. However, secretion of alpha(v), beta1 and alpha3 integrin molecules, which might play a role in implantation, was not affected.     

Endometrial integrin expression in women undergoing IVF and ICSI: a comparison of the two groups and fertile controls

BACKGROUND: Integrins are thought to play a vital role in implantation. Three integrins in particular (alpha(4)beta(1), alpha(v)beta(3) and alpha(1)beta(1)) are all present during the implantation window. Defects in their expression have been linked to tubal disease, unexplained infertility and endometriosis. Hence, a reduced endometrial integrin expression would be expected in women attending for IVF due to these causes of infertility when compared with those with male factor infertility attending for ICSI. METHODS: Women attending for IVF (n = 25) and ICSI (n = 25) treatment were recruited, and timed endometrial biopsies were taken during the 'implantation window' (cycle day 20-24). A group of fertile women (n = 15) attending for sterilization was used as controls. RESULTS: There was no significant difference in integrin expression between patients undergoing IVF or ICSI. Neither did these groups differ from the control group. CONCLUSIONS: The endometrium in patients undergoing ICSI treatment is sometimes thought to be more receptive, as the infertility might be due to a male factor. This study shows that there is no significant difference in integrin expression between patients attending for IVF or ICSI and the control group. These data add to the increasing uncertainty about the clinical value of assessing the endometrium with only one marker, in this case integrins.     

基质金属蛋白酶-9及其组织抑制物-1在妊娠输卵管黏膜中的表达

目的:检测基质金属蛋白酶-9(MMP-9)及其组织抑制物-1(TIMP-1)在输卵管黏膜中的表达,探讨与输卵管妊娠的关系。方法:采用免疫组织化学显色技术和图像半定量分析法,检测MMP-9和TIMP-1在人妊娠输卵管黏膜、人正常输卵管黏膜及正常宫内早孕子宫蜕膜组织中的表达。结果:MMP-9和TIMP-1在正常宫内早孕组中表达最强,在输卵管妊娠组中的表达较强,在正常输卵管组中表达较弱。两两比较差异均有显著性。结论:MMP-9/TIMP-1参与了输卵管妊娠中胚胎着床过程,且与输卵管妊娠缺乏蜕膜化反应有关。     

Expression of integrin alpha5 and integrin beta4 and their extracellular ligands fibronectin and laminin in human decidua during early pregnancy and its sex steroid-mediated regulation

The reorganization of the human endometrium is termed decidualization, which includes endometrial cell proliferation, differentiation, integrin switching and extracellular matrix (ECM) remodeling during early pregnancy. The present study aimed to investigate distribution patterns, staining intensity and sex steroid-mediated regulation of integrin alpha5 (CD49e), integrin beta4 (CD49f) expression and their ligands fibronectin and laminin during decidualization. Human tissue samples were evaluated in two groups, those collected in early days and those collected in advanced days of the first trimester. Correlating immunostaining was found between laminin and integrin beta4, and between fibronectin and integrin alpha5. The expression of fibronectin was higher than that of laminin in the early days (p < 0.05). Temporal and spatial immunostaining of integrin beta4 and alpha5 in the apical pole of luminal and glandular cells was observed as pregnancy progressed (p < 0.05). In vitro results showed that human chorionic gonadotropin (hCG) stimulated laminin expression, downregulated integrin beta4 expression, whereas estradiol decreased fibronectin expression by Ishikawa cells. hCG suppressed fibronectin expression in endometrial stromal cells in culture. Our results suggest that fibronectin is responsible for induction of decidual cell differentiation, and different temporal and spatial expression of the integrins may play a role in implantation. Our in vitro results suggest that regulation of extracellular matrix remodeling and integrin switching are at least partially regulated by reproductive hormones.     

Tubal ectopic pregnancy associated with an adenomatoid tumor

We present a case of coexistence of an ectopic pregnancy and an adenomatoid tumor in the same fallopian tube. The adenomatoid tumor is the most common benign neoplasm of the fallopian tube, and the vast majority of ectopic pregnancies occur in the fallopian tube. However, coexistence of these two conditions is extremely rare, and there has been only one previously reported case in the English literature. In the present case, the placental tissue, consisting of chorionic villi and decidua, was present in the ampulla, and the adenomatoid tumor was found in the myosalpinx, just proximal to the implantation site, replacing a large part of the myosalpinx. The close spatial relationship of these two lesions suggests that an adenomatoid tumor could have interfered with transportation of the fertilized ovum through the tube, possibly via impaired contractile activity of the myosalpinx, and consequently caused the ectopic tubal pregnancy.     

Integrins alpha4beta7 and alphaEbeta7 are expressed on epidermotropic T cells in cutaneous T cell lymphoma and spongiotic dermatitis.

Integrin alpha4beta7 has been associated with tissue-specific homing of malignant and inflammatory lymphocytes to gastrointestinal mucosa, whereas integrin alphaEbeta7 has been associated with intraepithelial lymphocytes in both the gut and the skin. This prompted us to examine the expression of alpha4beta7 on skin-infiltrating lymphocytes in 12 cases of patch/plaque stage cutaneous T cell lymphoma (CTCL) and in 4 cases of spongiotic dermatitis, which also display intraepidermal T cell accumulation. alpha4beta7 was found to be expressed on 64.8+/-7.4% of intraepidermal and 39.1+/-5.0% of intradermal T lymphocytes in CTCL. There was a significant positive correlation (r=0.58) between the degree of epidermotropism and the percentage of intraepidermal T cells expressing alpha4beta7. Similar findings were observed in spongiotic dermatitis, indicating that this result is not unique to malignant T cells. We evaluated staining of T cells in the same specimens for presence of alphaEbeta7 and observed a strong correlation between the expression of both beta7 integrins in each specimen. Staining with antibodies directed against the known ligands of alpha4beta7 was also performed on skin biopsies from CTCL patients. There was significantly increased dermal microvascular endothelial expression of vascular cell adhesion molecule-1 in lesional compared with nonlesional skin, and in nonlesional skin compared with skin of normal control subjects. Dermal and epidermal expression of the CS-1 domain of fibronectin was present but not increased in lesional biopsies compared with nonlesional or normal controls, whereas expression of mucosal addressin cell adhesion molecule-1 was not detectable in any skin biopsy specimens. In summary, alpha4beta7, like alphaEbeta7, is expressed at high levels on epidermotropic T cells and may interact with endothelial cell vascular cell adhesion molecule-1 as part of stepwise recruitment of lymphocytes from the blood to the epidermis.     

Characterization of integrin chains in normal and neoplastic human pancreas.

Integrins are a complex family of non-covalently linked heterodimeric glycoproteins which function as cell adhesion molecules, interacting with extracellular matrix molecules such as laminin, fibronectin, vitronectin, and collagen, and also having a role in intercellular adhesion. Each integrin subfamily is characterized by a common beta chain associated with variable alpha chains. We have examined, using immunohistological methods, the expression of the VLA (very late activation) family comprising beta 1 in association with alpha 1-6, and also alpha 6 in association with beta 4, the LFA beta chain beta 2, and the vitronectin receptor, in association with beta 1 or beta 5 and as the complex alpha v beta 3. Cryostat sections of normal pancreas, pancreatic adenocarcinomas, and ampullary tumours were studied together with six pancreatic carcinoma cell lines. Normal pancreas showed expression of beta 1 in all parenchyma. alpha 2 and alpha 6 had a similar distribution whereas alpha 3 expression was confined to ducts, including the very smallest radicles. Staining along the basement membranes of ducts was seen with beta 4 and the anti-vitronectin alpha v chain receptor antibody 13C2. Islet cells failed to stain with any antibody. No staining of epithelial components was seen with antibodies to alpha 1, alpha 4, alpha 5, or to the alpha v beta 3 form of the vitronectin receptor (beta 3 and alpha v beta 3 using the antibody 23C6). Pancreatic adenocarcinomas and ampullary tumours showed expression of alpha 2, alpha 3, alpha 6, beta 1, beta 4, and the vitronectin receptor (alpha v associated with beta 1 or beta 5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of biomaterial surface properties on fibronectin-alpha5beta1 integrin interaction and cellular attachment

The ability of fibronectin (Fn) to mediate cell adhesion through binding to alpha(5)beta(1) integrins is dependent on the conditions of its adsorption to the surface. Using a model system of alkylsilane SAMs with different functional groups (X=OH, COOH, NH(2) and CH(3)) and an erythroleukemia cell line expressing a single integrin (alpha(5)beta(1)), the effect of surface properties on the cellular adhesion with adsorbed Fn layers was investigated. (125)I-labeled Fn, a modified biochemical cross-linking/extraction technique and a spinning disc apparatus were combined to quantify the Fn adsorption, integrin binding and adhesion strength, respectively. This methodology allows for a binding equilibrium analysis that more closely reflects cellular adhesion found in stable tissue constructs in vivo. Differences in detachment strength and integrin binding were explained in terms of changes in the adhesion constant (psi, related to affinity) and binding efficiency of the adsorbed Fn for the alpha(5)beta(1) integrins (CH(3) approximately NH(2)相似文献   

Implantation-dependent expression of trophinin by maternal fallopian tube epithelia during tubal pregnancies: possible role of human chorionic gonadotrophin on ectopic pregnancy

Trophinin, tastin, and bystin have been identified as molecules potentially involved in human embryo implantation. Both trophoblasts and endometrial epithelial cells express trophinin, which mediates apical cell adhesion through homophilic trophinin-trophinin binding. We hypothesized that trophinin's function in embryo implantation is unique to humans and investigated the expression of trophinin, tastin, and bystin in ectopic pregnancy, a condition unique to humans. In tubal pregnancies, high levels of all three were found in both trophoblasts and fallopian tubal epithelia. Trophinin expression in maternal cells was particularly high in the area adjacent to the trophoblasts, whereas trophinin was barely detectable in intact fallopian tubes from women with in utero pregnancies or without pregnancies. When explants of intact fallopian tube were incubated with the human chorionic gonadotrophin (hCG), trophinin expression was enhanced in epithelial cells. Since the trophectoderm of the human blastocyst secretes hCG before and after implantation, these results suggest that hCG from the human embryo induces trophinin expression by maternal cells. As both beta-subunit of hCG and trophinin genes have diverged in mammals, the present study suggests a unique role of hCG and trophinin in human embryo implantation, including the pathogenesis of ectopic pregnancy.     

Distribution of integrin cell adhesion receptors in normal and malignant lung tissue.

The integrins are a family of transmembrane glycoproteins that serve as cell-cell and cell-substratum adhesion molecules and help regulate cellular morphology, differentiation, and proliferation. The integrin repertoire of a cell may therefore influence its behavior under resting conditions or following malignant transformation. For this reason, the distribution of integrins in normal lung tissues was determined using monoclonal antibodies against integrins of the beta 1 (VLA) and beta 3 (cytoadhesin) subfamilies and compared with the distribution in a limited number of lung carcinomas. The integrin subunits that bind to collagen and laminin (alpha 1, alpha 2, alpha 3, and alpha 6) and the alpha subunit, which can pair with beta 1, beta 3, or beta 5 and promote fibronectin, fibrinogen, or vitronectin binding, were the predominant integrins expressed on the major cell types of the lung, i.e., bronchial epithelium, vascular endothelium, and smooth muscle. Strong expression of the alpha 5 beta 1 fibronectin receptor and the beta 3 subunit was restricted to the endothelium of large vessels. Integrin expression by the lung carcinoma cells was somewhat heterogeneous; however, the tumors tended to express fewer integrins than did the normal bronchial epithelium.