Ultrastructural, Cellular, and Clinical Features of the Immotile-Cilia Syndrome

Palmblad, Jan; Mossberg, B; Afzelius, Björn A.

doi:10.1146/annurev.me.35.020184.002405

Cited by 53 publications

(21 citation statements)

References 24 publications

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“…A special type of human affliction called Kartagener's syndrome has been shown to result from absence of dynein arms in the cilia (Palmblad et al 1984) and to correlate with the absence of NO in nasal air (Lundberg et al 1994). Therefore, this syndrome may have a multifactorial pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Evidence for the NO cGMP Signaling Pathway In Respiratory Ciliated Epithelia of Rat

Zhan

Johns

1999

J Histochem Cytochem.

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SUMMARY Airway epithelia play a crucial role in protecting the lung from the external environment. Ciliated airway epithelial cells contribute to mucociliary transport systems via ciliary beating and electrolyte transport mechanisms to defend against respiratory tract infection. Both of these activities are regulated by nitric oxide (NO)-dependent mechanisms. To better understand the role of the NO-cGMP signal transduction cascade in these responses, we investigated the localization of endothelial nitric oxide synthase (eNOS), soluble guanylyl cyclase (sGC), cGMP-dependent protein kinase (PKG) I-␣ , and PKG I-␤ in the tracheas and lungs of normal rats by immunohistochemistry. Mouse anti-eNOS, rabbit antisGC, PKG I-␣ , and PKG I-␤ antibodies were used. Strong immunostaining for eNOS was detected in ciliated tracheal, bronchial, and bronchiolar epithelia, in Clara cells, and in Type II alveolar cells. The pattern of sGC and PKG I-␤ immunostaining showed striking parallels with that of eNOS staining. No staining was detectable in ciliated epithelium with the anti-PKG I-␣ antibody. Taken together, these observations suggest that PKG I-␤ might transduce NO-sGC signaling into biological responses in ciliated respiratory epithelia. N itrous oxide (NO) a physiologically important activator of sGC, plays an important regulatory role in airway function and is implicated in pulmonary physiology. There is evidence that ciliary beating and electrolyte transport are regulated by NO-dependent mechanisms (Jain et al. 1993(Jain et al. ,1995Takemura et al. 1995) and that eNOS is found in ciliated epithelia of rat lung and is specifically localized to the basal body of the microtubule of the cilia (Xue et al. 1996). Furthermore, low levels of nasal NO correlate with impaired mucociliary function in the upper airway (Lindberg et al. 1997), and NOS inhibitors decrease ciliary beating frequency (CBF) after prestimulation with isoproterenol, bradykinin, or substance P (Jain et al. 1993), indicating a novel NO-dependent mechanism that upregulates ciliary motility in response to stimulation. The role of cGMP as a mediator of NO signaling has recently focused attention on another area of investigation, the role of PKG and other potential cGMP receptor proteins in cell function. Surprisingly little is known about the mechanisms by which cGMP mediates the actions of NO. Both kinase-dependent and -independent actions of cGMP have been reported. The localization of PKG isoforms has been reported in kidney and other tissues (Gambaryan et al. 1996;Pryzwansky et al. 1995), but little is known of the localization of PKG in ciliated epithelium. Elucidating the presence and localization of PKG in ciliated epithelium would provide important information for understanding the signal transduction pathway for NO regulation. To better appreciate the "downstream" effects of NO cGMP signaling mechanisms in the lower airway and ciliated epithelium, we examined and localized eNOS, sGC, PKG I-␣ , and PKG I-␤ protein expression in rat trachea and lung tissues...

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical Evidence for the NO cGMP Signaling Pathway In Respiratory Ciliated Epithelia of Rat

Zhan

Johns

1999

J Histochem Cytochem.

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“…In addition, defects in the axonemes of spermatozoa isolated from Neuralized null mice result in immotile spermatozoa and male sterility. The axonemal and spermatid abnormalities seen in Neuralized null mice in part mimic the defects seen in many human spermatogenic disorders (32,45,46).…”

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confidence: 80%

Isolation of a Murine Homologue of the Drosophila neuralized Gene, a Gene Required for Axonemal Integrity in Spermatozoa and Terminal Maturation of the Mammary Gland

Vollrath

Pudney

Sylvia

et al. 2001

Molecular and Cellular Biology

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The Drosophila neuralized gene shows genetic interactions with Notch, Enhancer of split, and other neurogenic genes and is thought to be involved in cell fate specification in the central nervous system and the mesoderm. In addition, a human homologue of the Drosophila neuralized gene has been described as a potential tumor suppressor gene in malignant astrocytomas. We have isolated a murine homologue of the Drosophila and human Neuralized genes and, in an effort to understand its physiological function, derived mice with a targeted deletion of this gene. Surprisingly, mice homozygous for the introduced mutation do not show aberrant cell fate specifications in the central nervous system or in the developing mesoderm. This is in contrast to mice with targeted deletions in other vertebrate homologues of neurogenic genes such as Notch, Delta, and Cbf-1. Male Neuralized null mice, however, are sterile due to a defect in axoneme organization in the spermatozoa that leads to highly compromised tail movement and sperm immotility. In addition, female Neuralized null animals are defective in the final stages of mammary gland maturation during pregnancy.

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“…sia, is an autosomal dominant disease in which cilia lack motility as a result of the absence of dynein arms in the cilia (Palmblad et al 1984).…”

Section: Figurementioning

confidence: 99%

Expression of Endothelial Nitric Oxide Synthase in Ciliated Epithelia of Rats

Zhan

Johns

2003

J Histochem Cytochem.

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S U M M A R Y Endothelial nitric oxide synthase (eNOS), originally found in the endothelium of vascular tissue, also exists in other cell types, including ciliated epithelia of airways. The eNOS is ultrastructurally localized to the basal body of the microtubules of the cilia, and nitric oxide (NO) stimulates ciliary beat frequency (CBF). We examined whether the expression of eNOS is present in ciliated cells of other organs. Western blotting analysis revealed that eNOS was expressed in the rat cerebrum, lung, trachea, testis, and oviduct. Immunohistochemical staining showed that eNOS was localized in the ciliated epithelia of airways, oviduct, testis, and ependymal cells of brain in addition to the endothelium and smooth muscle of the vasculature. To confirm the activation of eNOS in the ciliated epithelia, we examined the effect of L -arginine (L-Arg), the substrate of NOS, on the production of nitrite and nitrate (NOx) in the cultured explants of rat trachea. L -Arg (100 M) increased NOx levels significantly ( p Ͻ 0.05). In explants exposed to inhibitors of NOS, the effect of L -Arg on the production of NOx was blocked. These findings suggest that epithelial NO plays an important role in signal transduction associated with ciliary functions.

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Ultrastructural, Cellular, and Clinical Features of the Immotile-Cilia Syndrome

Cited by 53 publications

References 24 publications

Immunohistochemical Evidence for the NO cGMP Signaling Pathway In Respiratory Ciliated Epithelia of Rat

Immunohistochemical Evidence for the NO cGMP Signaling Pathway In Respiratory Ciliated Epithelia of Rat

Isolation of a Murine Homologue of the Drosophila neuralized Gene, a Gene Required for Axonemal Integrity in Spermatozoa and Terminal Maturation of the Mammary Gland

Expression of Endothelial Nitric Oxide Synthase in Ciliated Epithelia of Rats

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