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Biomedical subjects

A Clement

Publications and source records attributed to A Clement.

At least 19 recordsLinked to original sources
PubMed1999

Role for NF-kappa B in mediating the effects of hyperoxia on IGF-binding protein 2 promoter activity in lung alveolar epithelial cells.

The surface of the pulmonary alveolus is a major target for oxidant injury, and its proper repair following injury is dependent on the proliferative response of the stem cells of the alveolar epithelium, the type 2 cells. In previous studies on the mechanisms controlling this response, we have documented involvement of several components of the IGF system, and mainly of the IGF binding protein-2 (IGFBP-2). We have provided evidence that this binding protein was associated with inhibition of DNA synthesis of type 2 cells exposed to oxidants and that its expression was regulated mostly at the level of transcription. In the present study, we focused on the factors involved in this regulation. From examination of the IGFBP-2 gene promoter sequence which revealed the presence of four potential binding sites for transcription factors of the NF-kappa B/Rel family, we hypothesized that NF-kappa B might be involved in the transcriptional activation of IGFBP-2 in oxidant-exposed cells. Data reported herein demonstrated that NF-kappa B activated IGFBP-2 promoter in transient transfection assays, and that exposure of cells to hyperoxia was associated with accumulation of the active form of NF-kappa B. Using gel shift analysis, we documented in O2-treated cells an increased binding to the four NF-kappa B binding sites. We also showed that accumulation of NF-kappa B was associated with a decrease in the inhibitory molecule I kappa B-alpha. Based on the current knowledge on NF-kappa B regulation, it is likely that in a number of situations associated with injury of lung alveolar epithelial cells signaling events involving accumulation of NF-kappa B converge to activate IGFBP-2 and to block entry into S phase.

Animals↗
PubMed1998

Differential interactions of MAP2, tau and MAP5 during axogenesis in culture.

The subcellular interactions of the neuronal microtubule-associated proteins tau, MAP2 and MAP5 were determined in cultured rat hippocampal neurons using differential detergent extraction and laser scanning microscopy. Axon development correlated with a transition from a MAP2-actin filament interaction to a MAP2-microtubule association and binding of tau to the distal axon. Tau and MAP2 binding specifically increased in the axon and the minor neurites, respectively. No compartment-specific association of MAP5 was observed. Tau binding preceded the accumulation of microtubules at the distal axon which represented a characteristic event during axogenesis. The data provide evidence for a role of MAP2 in regulating microfilament-microtubule interactions during neurite formation and of tau in organizing microtubules at the distal axon.

Animals↗
PubMed1998

Characteristic hexasaccharide sequences in octasaccharides derived from shark cartilage chondroitin sulfate D with a neurite outgrowth promoting activity.

A mouse brain chondroitin sulfate (CS) proteoglycan, DSD-1-PG, bears the DSD-1 epitope and has neurite outgrowth promoting properties. Shark cartilage CS-C inhibits the interactions between the DSD-1-specific monoclonal antibody 473HD and the CS chains of the DSD-1-PG, which is expressed on the mouse glial cells (Faissner, A., Clement, A., Lochter, A., Streit, A., Mandl, C., and Schachner, M. (1994) J. Cell Biol. 126, 783-799). On the other hand, several hexasaccharides isolated from commercial shark cartilage CS-D, which contains a higher proportion of characteristic D units (GlcUA(2-sulfate)beta1-3GalNAc(6-sulfate)) as compared with CS-C, has the A-D tetrasaccharide sequence composed of an A disaccharide unit (GlcUAbeta1-3GalNAc(4-sulfate)) and a D disaccharide unit (Nadanaka, S. and Sugahara, K. (1997) Glycobiology 7, 253-263). In this study, the biological activities and the structure of shark cartilage CS-D were investigated. CS-D inhibited the interactions between monoclonal antibody 473HD and DSD-1-PG and also promoted neurite outgrowth of embryonic day 18 hippocampal neurons. Eight octasaccharide fractions were isolated from CS-D after partial digestion with bacterial chondroitinase ABC by means of gel filtration chromatography and anion-exchange high performance liquid chromotography to investigate the frequency and the arrangement of the A-D tetrasaccharide unit in the polymer sequence. Structural analysis performed by a combination of enzymatic digestions with 500-MHz 1H NMR spectroscopy demonstrated that the isolated octasaccharides shared the common core structure DeltaHexAalpha1-3GalNAcbeta1-4(GlcUAbeta1-3GalNAc)3 with four, five, and six sulfate esters at various hydroxyl groups in different combinations. In the structure, DeltaHexA and GlcUA represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid and glucuronic acid, respectively. No D-D tetrasaccharide sequence was found, and discrete D disaccharide units were demonstrated exclusively as A-D tetrasaccharide units in either an A-D-A or an A-D-C hexasaccharide sequence in the five octasaccharides that represented about 5.0% (w/w) of the starting polysaccharides (C denotes the disaccharide GlcUAbeta1-3GalNAc(6-sulfate)). It remains to be determined whether such characteristic hexasaccharide sequences present in shark cartilage CS-D serve as functional domain structures recognized by some protein ligands.

Animals↗
PubMed1998

Chronic interstitial lung disease in children: response to high-dose intravenous methylprednisolone pulses.

The prognosis for children with chronic interstitial lung disease is poor and the mortality rate is high, especially in infants. This explains the many therapeutical protocols which have been proposed and investigated by several authors. In the present work, we evaluated the response of three infants with idiopathic pulmonary fibrosis to high-dose intravenous prednisolone pulses. The patients were referred to the department at the age of 4, 17, and 3 months, respectively. The diagnosis was confirmed by open lung biopsy and intravenous pulse methyl prednisolone therapy was started with the following protocol: 300 mg/m2 methylprednisolone daily for 3 days, repeated every 4 to 6 weeks. Because of the extreme severity of the respiratory distress at the time of diagnosis, the intravenous pulse treatments were initially complemented by oral prednisone. Clinical improvement was noticed within 6 months with progressive correction of hypoxemia. After follow-up for 3.5 to 4 years, with a total number of pulses of 37, 26, and 32, respectively, the children are symptom-free and do not require oxygen supplementation. During this period, no side effects and no adrenal insufficiency could be documented. Based on current knowledge of steroid action, it can be speculated that the response to intermittent high-dose intravenous methylprednisolone may explain the ability of this mode of hormone administration to maintain an adequate level of glucocorticoid receptor expression. More information and trials through multicenter collaborations are needed to assess therapeutical protocols of repeated high-dose intravenous steroid treatment.

Adolescent↗
PubMed1998

Effect of hyperoxia on human macrophage cytokine response.

In the development of lung damage induced by oxidative stress, it has been proposed that changes in alveolar macrophages (AM) function with modifications in cytokine production may contribute to altered repair processes. To characterize the changes in profiles of cytokine production by macrophages exposed to oxidants, the effects of hyperoxia (95% O2) on interleukin (IL)-1 beta, IL-6, IL-8, and tumour necrosis factor-alpha (TNF-alpha) expression were studied. Experiments were first performed using AM obtained from control subjects and children with interstitial lung disease. Results showed that a 48 h O2 exposure was associated with two distinct patterns of response: a decrease in TNF-alpha, IL-1 beta and IL-6 expression, and an increase in IL-8. To complete these observations we used U937 cells that were exposed for various durations to hyperoxia. We confirmed that a 48 h O2 exposure led to similar changes with a decrease in TNF-alpha, IL-1 beta and IL-6 production and an increase in IL-8. Interestingly, this cytokine response was preceded during the first hours of O2 treatment by induction of TNF-alpha, IL-1 beta and IL-6. These data indicate that hyperoxia induces changes in the expression of macrophages inflammatory cytokines, and that these modifications appear to be influenced by the duration of O2 exposure.

Bronchoalveolar Lavage Fluid↗
PubMed1998

Retinoic acid-induced proliferation of lung alveolar epithelial cells: relation with the IGF system.

Retinoids, including retinol and retinoic acid (RA) derivatives, are important molecules for lung growth and homeostasis. The presence of RA receptors and of RA-binding proteins in the alveolar epithelium led to suggest a role for RA on alveolar epithelial cell replication. In the present study, we examined the effects of RA on proliferation of the stem cells of the alveolar epithelium, the type 2 cells. We showed that treatment of serum-deprived type 2 cells with RA led to a stimulation of cell proliferation, with an increase in cell number in a dose-dependent manner. To gain some insights into the mechanisms involved, we studied the effects of RA on the expression of several components of the insulin-like growth factor (IGF) system that have been shown to be associated with the growth arrest of type 2 cells, mainly the IGF-binding protein-2 (IGFBP-2), IGF-II, and the type 2 IGF receptor. We documented a marked decrease in the expression of these components upon RA treatment. Using conditioned media from RA-treated cells, we provided evidence that the proliferative response of type 2 cells to RA was mediated through production of growth factor(s) distinct from IGF-I. We also showed that RA was able to reduce the decrease in cell number observed when type 2 cells were treated with transforming growth factor (TGF)-beta1. These results together with the known stimulatory effect of TGF-beta1 on IGFBP-2 expression led to suggest that RA may be associated with type 2 cell proliferation through mechanisms interfering with the TGF-beta1 pathway.

Animals↗
PubMed1998

Expression of insulin-like growth factors and their binding proteins by bronchoalveolar cells from children with and without interstitial lung disease.

The involvement of the insulin-like growth factor (IGF) system in lung growth and repair following injury is sustained by a number of studies. Based on this knowledge, the aim of the present work was to document the expression of the IGFs and their binding proteins by alveolar cells obtained by bronchoalveolar lavage (BAL). Two groups were investigated: a control group of five children and a group of 11 children referred to the department for exploration of interstitial lung disease (ILD). Components of the IGF system studied included IGF-I, IGF-II and IGF-binding proteins (IGFBP). Expression of these factors was analysed at the level of messenger ribonucleic acid (mRNA) (by semi-quantitative reverse transcription polymerase chain reaction techniques), and of protein for the IGFBPs. In addition, expression of two major cytokines associated with the inflammatory process, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), was also documented. In children without parenchymal disease, the growth factor expressed was IGF-I, in association with the presence of mRNA for IGFBP-2 in all cases. In children with ILD, expression of IGF-I was observed in nine patients and of IGF-II in three patients, and the presence of IGFBP-2 was found in all extracts analysed (mRNA and proteins). Evaluation of IGFBP-2 expression indicated an increase in the group of children with ILD. Interestingly, a significant association was observed between the increase in IGFBP-2 expression and TGF-beta expression. The present data emphasize the presence on insulin-like growth factor-binding protein-2 in the BAL of all patients, and suggest that this protein may be an important factor of the injury/repair processes during the progression of alveolar inflammation.

Adolescent↗
PubMed1997

Mapping of a defined neurocan binding site to distinct domains of tenascin-C.

Neurocan is a member of the aggrecan family of proteoglycans which are characterized by NH2-terminal domains binding hyaluronan, and COOH-terminal domains containing C-type lectin-like modules. To detect and enhance the affinity for complementary ligands of neurocan, the COOH-terminal neurocan domain was fused with the NH2-terminal region of tenascin-C, which contains the hexamerization domain of this extracellular matrix glycoprotein. The fusion protein was designed to contain the last downstream glycosaminoglycan attachment site and was expressed as a proteoglycan. In ligand overlay blots carried out with brain extracts, it recognized tenascin-C. The interaction was abolished by the addition of EDTA, or TNfn4,5, a bacterially expressed tenascin-C fragment comprising the fourth and fifth fibronectin type III module. The fusion protein directly reacted with this fragment in ligand blot and enzyme-linked immunosorbent assay procedures. Both tenascin-C and TNfn4,5 were retained on Sepharose 4B-linked carboxyl-terminal neurocan domains, which in BIAcore binding studies yielded a KD value of 17 nM for purified tenascin-C. We conclude that a divalent cation-dependent interaction between the COOH-terminal domain of neurocan and those fibronectin type III repeats is substantially involved in the binding of neurocan to tenascin-C.

Amino Acid Sequence↗
PubMed1997

Idiopathic pulmonary fibrosis in infants.

Idiopathic pulmonary fibrosis is a poorly characterized disease in infants. In the present report, we reviewed our experience with 10 infants during a 10-year period. In 9 patients, onset of symptoms occurred before the age of 2 months and included tachypnea, cough, and inadequate weight gain. However, despite the presence of these symptoms, diagnosis was delayed for 3 months at which time the infants were referred to the pediatric pulmonary department, when the diagnosis was confirmed by open lung biopsy. At the time of admission, bronchoscopy with alveolar lavage was performed in 9 children and showed severe alveolitis with an increase in the neutrophil count. Nine infants were treated with prednisone alone or in combination with chloroquine, colchicine, or cyclophosphamide; all these patients died despite treatment. One infant was treated with pulses of methylprednisolone because of a failure in response to oral prednisone. This girl who displayed similar clinical, radiological, and histological abnormalities as the other children at the time of diagnosis is the only child still alive after 3 years of follow-up. She is now free of respiratory symptoms and has a normal growth curve. The present report raised two important points: (1) a thorough evaluation of characteristic symptoms should lead to an early diagnosis of pulmonary fibrosis in infants; and (2) administration of pulse therapy using corticosteroids has been helpful and needs to be evaluated further.

Biopsy↗
PubMed1997

Involvement of the cell cycle inhibitor CIP1/WAF1 in lung alveolar epithelial cell growth arrest induced by glucocorticoids.

Glucocorticoids are known to impair the postnatal development of lung parenchyma by altering the formation of alveoli, and from the current understanding of the processes controlling the growth of the alveolar structure, it is likely that this impairment relies in large part on alteration of alveolar epithelial cell replication. From recent studies on the modulation of cell proliferation by glucocorticoids, it appears that events associated with the G1 phase of the cell cycle are a major target for the actions of these hormones. To gain some insights into the mechanisms involved in the growth arrest of lung alveolar epithelial cells by glucocorticoids, we focused in the present study on the effects of these hormones on the expression of the G1 cyclins and their cell cycle-dependent kinases (CDKs). We observed that when cells were blocked in their proliferation by dexamethasone treatment, no changes in the expression of the various G1 cyclins, D1, D2, D3, or E, could be documented. Also, the levels of CDK2 and CDK4 in glucocorticoid-treated cells did not exhibit significant modifications compared with the levels in proliferating cells. Evaluation of the activity of cyclin-CDK complexes showed that activation of cyclin D-CDK4 was not modified by dexamethasone. By contrast, differences in the activity of cyclin E-CDK2 complexes were found, with a profound decrease in the extracts of cells growth arrested by dexamethasone. Studies of the factors potentially implicated in the inactivation of these complexes strongly suggested a role for p21CIP1, as a dramatic accumulation of this protein was observed in cells treated with dexamethasone. Moreover, changes in p21CIP1 expression appeared to be controlled mostly at the posttranscriptional level. Interestingly, a decrease in the levels of p27KIP1 could be observed. These results indicate that glucocorticoids block entry of alveolar epithelial cells into S phase by specifically altering the activation of cyclin E-CDK2 complexes through induction of the CDK inhibitor p21CIP1.

Animals↗
PubMed1996

Altered regulation of G1 cyclins in oxidant-induced growth arrest of lung alveolar epithelial cells. Accumulation of inactive cyclin E-DCK2 complexes.

The alveolar surface of the lung is a major target for oxidant injury, and its repair following injury is dependent on the ability of its stem cells, the type 2 cells, to initiate proliferation. From previous studies it is likely that events located before the entry into the S phase of the cell cycle and involving several components of the insulin-like growth factor system as well as of transforming growth factor-beta (TGF-beta) play a key role in growth regulation of oxidant-exposed type 2 epithelial cells. To gain further insights into these mechanisms, we explored the effects of O2 exposure on G1 cyclins and their cyclin-dependent kinases (CDKs). We documented an increased expression of these genes in O2-treated type 2 cells. However, despite this induction, a dramatic decrease in cyclin E-CDK2 activity, but not in cyclin D-CDK4 activity, was found. The concomitant induction of CDK inhibitory proteins (CKIs), mainly p21(CIP1), suggests that accumulation of inactive cyclin E-CDK2 activity is due to CKI binding. We also provided evidence that the mechanisms regulating this process involved TGF-beta as anti-TGF-beta antibody treatment was able to reduce the oxidant-induced inhibition of cyclin E-CDK2 activity. Taken together, these results suggest that oxidants may block entry into S phase by acting on a subset of late G1 events whose alterations are sufficient to impair the activation of cyclin E-CDK2 complexes.

Animals↗
PubMed1996

Tau binds to the distal axon early in development of polarity in a microtubule- and microfilament-dependent manner.

Microtubule-associated protein tau is localized to the axon in situ and has been implicated in the development of neuronal polarity. Here we report that tau is extracted differentially in cultured hippocampal neurons yielding an axon-specific localization under conditions that keep the integrity of the plasma membrane. The amount of bound tau increases toward the distal axon and is highest at the transition from the axonal shaft to the growth cone. This distribution is significantly different from the distribution of axonal microtubules that are most concentrated at the proximal axon. Distal binding of tau to one process appears early in development of polarity in culture and correlates with the onset of axon formation (day 2 in culture). Binding to the distal axon requires intact microtubules and microfilaments. Distal tau binding does not stabilize microtubules selectively against drug-induced disassembly, because colchicine-induced microtubule depolymerization is highest distally. We conclude that binding of tau to the distal axon follows a complex mechanism, is an early event in the development of polarity, and reproduces the axon-specific localization of tau in situ.

Actin Cytoskeleton↗
PubMed1996

Rat lung alveolar type II cell line maintains sodium transport characteristics of primary culture.

Culture of primary alveolar type II cells has been widely used to investigate the Na+ transport characteristics of alveolar epithelium. However, this model was restricted by early morphological and physiological dedifferentiation in culture. Recently, a cell line has been obtained by transfection of neonatal type II cells with the simian virus SV40 large T antigen gene (SV40-T2). SV40-T2 cells have retained proliferative characteristics of the primary type II cells (Clement et al., 1991, Exp. Cell Res., 196:198-205.) In the present study, we have characterized Na+ transport pathways in SV40-T2 cells. SV40-T2 cells retained most cardinal properties of the original alveolar epithelial cells. Na+ entry occurred, as in primary cultures, through both Na(+)-cotransporters and amiloride-sensitive Na+ channels. SV40-T2 cells expressed Na(+)-phosphate. Na(+)-amino acid and Na(+)-K(+)-Cl cotransports which are quantitatively similar to that of primary cultures. The existence of amiloride-sensitive Na+ channels was supported by molecular and functional data. SV40-T2 expressed the cloned alpha- and gamma-mRNAs for the rat epithelial Na+ channel (rENaC), whereas beta subunit was not detected, and 22Na+ influx was significantly inhibited by 10 microM amiloride. Na+, which enters SV40-T2 cells, is extruded through a Na+, K(+)-ATPase: mRNA for alpha 1 and beta 1 isoforms of Na+, K(+)-ATPase were present and Na+, K(+)-ATPase activity was evidenced either on intact cells by the presence of a ouabain-sensitive component of 86Rb+ influx or on cell homogenates by the measurement of ouabain-inhibitable ATP hydrolysis. These results indicate that SV40-T2 cell line displays most of the Na+ transport characteristics of well-differentiated primary cells in the first days of culture. We conclude that the SV40-T2 cell line provides a model of differentiated alveolar type II cells and may be a powerful tool to study, in vitro, the modulation of Na+ transport in pathophysiological conditions.

Amiloride↗
PubMed1996

Tenascin-C contains distinct adhesive, anti-adhesive, and neurite outgrowth promoting sites for neurons.

The glia-derived extracellular matrix glycoprotein tenascin-C (TN-C) is transiently expressed in the developing CNS and may mediate neuron-glia interactions. Perturbation experiments with specific monoclonal antibodies suggested that TN-C functions for neural cells are encoded by distinct sites of the glycoprotein (Faissner, A., A. Scholze, and B. Götz. 1994. Tenascin glycoproteins in developing neural tissues--only decoration? Persp. Dev. Neurobiol. 2:53-66). To characterize these further, bacterially expressed recombinant domains were generated and used for functional studies. Several short-term-binding sites for mouse CNS neurons could be assigned to the fibronectin type III (FNIII) domains. Of these, the alternatively spliced insert TNfnA1,2,4,B,D supported initial attachment for both embryonic day 18 (E18) rat and postnatal day 6 (P6) mouse neurons. Only TNfn1-3 supported binding and growth of P6 mouse cerebellar neurons after 24 h, whereas attachment to the other domains proved reversible and resulted in cell detachment or aggregation. In choice assays on patterned substrates, repulsive properties could be attributed to the EGF-type repeats TNegf, and to TNfnA1,2,4. Finally, neurite outgrowth promoting properties for E18 rat hippocampal neurons and P0 mouse DRG explants could be assigned to TNfnB,D, TNfnD,6, and TNfn6. The epitope of mAb J1/tn2 which abolishes the neurite outgrowth inducing effect of intact TN-C could be allocated to TNfnD. These observations suggest that TN-C harbors distinct cell-binding, repulsive, and neurite outgrowth promoting sites for neurons. Furthermore, the properties of isoform-specific TN-C domains suggest functional significance of the alternative splicing of TN-C glycoproteins.

Amino Acid Sequence↗
PubMed1996

Glucocorticoid-induced growth arrest of lung alveolar epithelial cells is associated with increased production of insulin-like growth factor binding protein-2.

Glucocorticoids have been shown to impair lung growth by altering development of the alveolar structure. To characterize the mechanisms involved in this process, we examined the effects of dexamethasone on proliferation of the stem cells of the alveolar epithelium, the type 2 cells. Treatment of type 2 cells with dexamethasone rapidly decreased DNA synthesis, and this effect was observed for concentrations less than 10(-8)M. Inhibition of cell proliferation by glucocorticoids was associated with a marked accumulation of insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) in the culture medium. Studies of the mechanisms involved in this accumulation indicated that it was associated with an enhanced production of IGFBP-2 and with a similar increase in the level of IGFBP-2 messenger RNA expression without any changes in its stability, as evaluated by actinomycin D experiments. Furthermore, transfection studies using plasmids conveying expression of luciferase gene transcribed from the fragment of rat IBFBP-2 promoter extending from +12 bp relative to the start of transcription plus 1.4 kilobases of the 5'-flanking sequence showed a stimulation of luciferase activity in cells treated with dexamethasone that was similar to the increase in IGFBP-2 messenger RNA and protein. Study of the other components of the IGF system also revealed induction of IGF-II expression upon treatment with dexamethasone. Together with other previously reported results using various modulators of type 2 cell proliferation, the present study strongly suggests that IGFBP-2 is likely to play an important role in the control of alveolar epithelial cell proliferation.

Animals↗
PubMed1996

BAL in children: a controlled study of differential cytology and cytokine expression profiles by alveolar cells in pediatric sarcoidosis.

STUDY OBJECTIVE: The development of BAL in children for both research and clinical purposes has been limited so far by the difficulty in establishing reference values. The aim of the study was (1) to define composition of BAL cellular components in control children and to evaluate the ability of these cells to express various cytokines, and (2) to study modifications of differential cytology and BAL cell cytokine responses in children with interstitial lung disorders. POPULATIONS AND METHODS: Two groups were investigated: a control group of 16 children who were concluded to be free of parenchymal lung disease after complete pulmonary investigation, and a group of 11 children with pulmonary sarcoidosis. Differential cytology was evaluated by standard techniques. BAL cell cytokine expression was studied at the level of messenger RNA (mRNA) by reverse transcription-polymerase chain reaction (RT-PCR) methods. RESULTS: In the control group, differential cell counts appeared to be similar to values reported in adult populations with normal distribution of the data and no influence of age. In this group, no transcripts for interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and transforming (correction of tranforming) growth factor-beta (TGF-beta) could be detected. In children with sarcoidosis, different profiles of IL-1beta, TNF-alpha, IL-6, and TGF-beta expression were individualized which seemed to be related to the activity and/or severity of the disease, IL-6 and TGF-beta mRNA being observed only in the more severe forms. CONCLUSION: These data provide information on BAL cell number and function in children. Characterization of BAL cytokine expression patterns during the course of interstitial lung diseases in children may be of great interest for evaluation of disease activity and/or severity and therefore for planning of therapy.

Actins↗
PubMed1995

Expression of insulin-like growth factor receptors 1 and 2 in the developing lung and their relation to epithelial cell differentiation.

Insulin-like growth factors (IGFs) and their receptors have been implicated as regulators of cell differentiation and cell proliferation in a number of systems and have been shown to play an important role in embryonic development. In this study we examined expression of mRNA for IGF-I and IGF-II, IGF binding protein 2 (IGFBP-2), and IGF receptors 1 (IGFR-1) and 2 (IGFR-2) during fetal lung development and in early postnatal and adult lungs by the polymerase chain reaction (PCR). IGF-I mRNA was found in embryonic and postnatal lungs at all ages as was IGFBP-2, whereas IGF-II mRNA was present only in prenatal lungs. IGFR-1 was present in all but the adult lungs. Lung epithelial cells expressed IGFR-1 at 14 days' gestation but not at 18 days' gestation as measured by PCR and in situ hybridization. Alveolar epithelial cells re-expressed IGFR-1 mRNA in the early postnatal period but not in the adult lung. IGFR-2 was expressed by PCR and in situ hybridization in 14-day embryonic epithelium, was not present at 18 days or at birth, but was re-expressed at high levels in the early postnatal alveolar wall. Immunocytochemical localization of IGFR-2 confirmed its absence in the late fetal and newborn lung. It reappeared in alveoli, exclusively in type 1 cells, in early postnatal and adult lungs. These studies demonstrate the stage- and cell-specific appearance of IGF receptors in the developing and postnatal lung. They also establish IGFR-2 as a marker of the mature alveolar type 1 cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗